natriuretic-peptide--brain and Diabetes-Mellitus--Type-2

This systematic review and meta-analysis aimed at summarizing the existing clinical evidence to evaluate the prognostic performance of N-terminal prohormone brain natriuretic peptide (NT-proBNP) in predicting cardiovascular events, cardiovascular-related mortality, and all-cause mortality in patients with type 2 diabetes.. Searches were performed in Medline, Embase, Scopus, and Web of Science databases before August 1, 2021. The data were recorded as adjusted hazard ratio (HR).. An increase in NT-proBNP increases the risk of cardiovascular events (HR = 1.63), cardiovascular mortality (HR = 1.86) and all-cause mortality (HR = 1.54). Seemingly, the best cutoffs for predicting cardiovascular events (HR = 2.30) and cardiovascular mortality (HR = 3.77) are levels greater than 100 pg/mL. The best cutoff of NT-proBNP in predicting all-cause mortality is levels greater than 225 pg/mL (HR = 4.72).. A moderate level of evidence demonstrated that NT-proBNP serum levels can predict future cardiovascular events, cardiovascular mortality, and all-cause mortality. Thus, it can be used as risk stratification for type 2 diabetes.

Topics: Biomarkers; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Risk Assessment

Whether an antidiabetic drug, glucagon-like peptide-1 receptor agonist (GLP-1RA), could improve the prognosis of heart failure and cardiac function remains controversial. We conducted a systematic review and meta-analysis of randomized controlled trials to explore the influence of GLP-1RAs on heart failure in patients regardless of diabetes diagnosis.. Literature in English from the PubMed, EMBASE, and Cochrane Library databases was searched from inception to July 2022. The study aim was to identify published, randomized, placebo-controlled trials testing GLP-1RAs in patients with or without diabetes. Outcomes were heart failure hospitalization, cardiac function, and structure measures.. Twenty-two randomized controlled trials involving 61,412 patients are included in the meta-analysis. Overall, compared with the placebo group, GLP-1RA treatment could not significantly decrease heart failure hospitalization in patients with a history of heart failure (hazard ratio [HR], 1.07; 95% CI, 0.91 to 1.25; P = 0.422). Six-minute walking test distances (WMD, 19.08 m; 95% CI, 4.81 to 33.36; P = 0.01), E-wave (SMD, -0.40; 95% CI, -0.60 to -0.20; P < 0.001), early diastolic to late diastolic velocities ratio (WMD, -0.10; 95% CI, -0.18 to -0.02; P = 0.01), mitral inflow E velocity to tissue Doppler e' ratio (WMD, -0.97; 95% CI, -1.54 to -0.41; P < 0.001), and E-wave deceleration time (WMD, -9.96 milliseconds; 95% CI, -18.52 to -1.41; P = 0.02) increased significantly after administration of GLP-1RAs. However, GLP-1RAs do not significantly influence N-terminal pro-B-type natriuretic peptide levels (WMD, -20.02 pg/mL; 95% CI, -53.12 to 13.08; P = 0.24), Minnesota Living with Heart Failure Questionnaire quality of life scores (WMD, -1.08; 95% CI, -3.99 to 1.84; P = 0.47), or left ventricular ejection fractions (WMD, -0.37%; 95% CI, -1.19 to 0.46; P = 0.38).. GLP-1RAs did not reduce heart failure readmissions in patients with a history of heart failure and elevated N-terminal pro-B-type natriuretic peptide levels. Thus, the prognosis of heart failure was not improved, although GLP-1RAs did significantly improve left ventricular diastolic function in patients. PROSPERO identifier: CRD42021226231.

Topics: Diabetes Mellitus, Type 2; Glucagon-Like Peptide-1 Receptor; Heart Failure; Humans; Hypoglycemic Agents; Natriuretic Peptide, Brain; Prognosis; Quality of Life; Randomized Controlled Trials as Topic

Glucagon-like peptide 1 receptor agonists (GLP-1RA) decrease the risk of major adverse cardiovascular events (MACE). However, their influence on the risk of heart failure (HHF) hospitalization is marginal, which is unexpected given their benefits on cardiometabolic risk, especially on bodyweight reduction. This meta-analysis aimed to map the effects of GLP-1RA on N-terminal pro-BNP.. We retrieved from a Medline and Embase all randomized trials comparing GLP-1RA with placebo, reporting NT-proBNP concentrations. The primary outcome was the change in N-terminal pro-BNP values from baseline to end-of-treatment with GLP-1RA versus placebo (reported as standard deviations, SD). We included nine trials (543 patients in active treatment and 536 in placebo). We observed significantly greater reductions in N-terminal pro-BNP with GLP-1RA versus placebo (-0.14 SD; 95% CI -0.27; -0.01; p = 0.03). Upon meta-regression, no modifying effect of age, HbA1c, and body mass index were observed, nor was any meta-correlation between the change in NT-proBNP and the change in HbA1c or body weight.. GLP-1RA can significantly decrease N-terminal pro-BNP. This effect was independent of baseline age, body weight, and metabolic control.

Topics: Body Weight; Diabetes Mellitus, Type 2; Glucagon-Like Peptide-1 Receptor; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Natriuretic Peptide, Brain; Peptide Fragments

Type 2 diabetes is one of the most relevant risk factors for heart failure, the prevalence of which is increasing worldwide. The aim of the review is to highlight the current perspectives of the pathophysiology of heart failure as it pertains to type 2 diabetes. This review summarizes the proposed mechanistic bases, explaining the myocardial damage induced by diabetes-related stressors and other risk factors, i.e., cardiomyopathy in type 2 diabetes. We highlight the complex pathology of individuals with type 2 diabetes, including the relationship with chronic kidney disease, metabolic alterations, and heart failure. We also discuss the current criteria used for heart failure diagnosis and the gold standard screening tools for individuals with type 2 diabetes. Currently approved pharmacological therapies with primary use in type 2 diabetes and heart failure, and the treatment-guiding role of NT-proBNP are also presented. Finally, the influence of the presence of type 2 diabetes as well as heart failure on COVID-19 severity is briefly discussed.

Topics: Biomarkers; COVID-19; Diabetes Mellitus, Type 2; Disease Management; Glycated Hemoglobin; Heart Failure; Humans; Mass Screening; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis

Topics: Benzhydryl Compounds; Diabetes Mellitus, Type 2; Glucosides; Heart Failure; Humans; Kidney Diseases; Natriuretic Peptide, Brain; Peptide Fragments; Randomized Controlled Trials as Topic; Sodium-Glucose Transporter 2 Inhibitors

Patients with Type 2 diabetes have an excess risk for cardiovascular disease. One of the several approaches, included in the guidelines for the management of Type 2 diabetes, is based on dipeptidyl peptidase 4 (DPP-4; also termed CD26) inhibitors, also called gliptins. Gliptins inhibit the degradation of glucagon-like peptide-1 (GLP-1): this effect is associated with increased circulating insulin-to-glucagon ratio, and a consequent reduction of HbA1c. In addition to incretin hormones, there are several proteins that may be affected by DPP-4 and its inhibition: among these some are relevant for the cardiovascular system homeostasis such as SDF-1α and its receptor CXCR4, brain natriuretic peptides, neuropeptide Y and peptide YY. In this review, we will discuss the pathophysiological relevance of gliptin pleiotropism and its translational potential.

Topics: Cardiovascular Diseases; Cardiovascular System; Chemokine CXCL12; Diabetes Mellitus, Type 2; Dipeptidyl Peptidase 4; Dipeptidyl-Peptidase IV Inhibitors; Glucagon; Glucagon-Like Peptide 1; Glycated Hemoglobin; Humans; Insulin; Natriuretic Peptide, Brain; Neuropeptide Y; Practice Guidelines as Topic; Proteolysis; Receptors, CXCR4

Atrial and B-type Natriuretic Peptides (NP) are cardiac hormones with potent cardiovascular and metabolic effects. They signal through the NPRA/cGMP system and are inactivated by a clearance receptor NPRC and neutral endopeptidases (NEP). Recombinant ANP and BNP are currently used as drug treatment for acute decompensated congestive heart failure. Recent literature indicate that a defective NP system is linked to obesity and predict the risk of type 2 diabetes (T2D). Areas covered: This article reviews recent epidemiological, clinical and preclinical evidences that NP system deficiency may be causal of obesity and T2D. The molecular mechanisms of the NP pathway in several metabolic target tissues are presented. The therapeutic potential of NP in obesity and T2D is discussed. Expert opinion: Targeting the NP pathway may offer a novel therapeutic avenue for the management of obesity and T2D. The benefit/risk of drugs increasing circulating NP levels by blocking NPRC and NEP, and/or enhancing NPRA signaling should be assessed in obese and type 2 diabetic individuals.

Topics: Animals; Atrial Natriuretic Factor; Diabetes Mellitus, Type 2; Humans; Molecular Targeted Therapy; Natriuretic Peptide, Brain; Neprilysin; Obesity; Receptors, Atrial Natriuretic Factor

This study assessed the effect of GLP-1 based therapies on atherosclerotic markers in type 2 diabetes patients. 31 studies were selected to obtain data after multiple database searches and following inclusion and exclusion criteria. Age and BMI of the participants of longitudinal studies were 59.8 ± 8.3 years and 29.2 ± 5.7 kg/m(2) (Mean±SD). Average duration of GLP-1 based therapies was 20.5 weeks. Percent flow-mediated diameter (%FMD) did not change from baseline significantly but when compared to controls, %FMD increased non-significantly following GLP-1-based therapies (1.65 [-0.89, 4.18]; P = 0.2; REM) in longitudinal studies and increased significantly in cross sectional studies (2.58 [1.68, 3.53]; P < 0.00001). Intima media thickness decreased statistically non-significantly by the GLP-1 based therapies. GLP-1 based therapies led to statistically significant reductions in the serum levels of brain natriuretic peptide (-40.16 [-51.50, -28.81]; P < 0.0001; REM), high sensitivity c-reactive protein (-0.27 [-0.48, -0.07]; P = 0.009), plasminogen activator inhibitor-1 (-12.90 [-25.98, 0.18]; P=0.05), total cholesterol (-5.47 [-9.55, -1.39]; P = 0.009), LDL-cholesterol (-3.70 [-7.39, -0.00]; P = 0.05) and triglycerides (-16.44 [-25.64, -7.23]; P = 0.0005) when mean differences with 95% CI in the changes from baselines were meta-analyzed. In conclusion, GLP-1-based therapies appear to provide beneficial effects against atherosclerosis. More randomized data will be required to arrive at conclusive evidence.

Topics: Aged; C-Reactive Protein; Carotid Intima-Media Thickness; Cholesterol; Cholesterol, LDL; Databases, Factual; Diabetes Mellitus, Type 2; Female; Glucagon-Like Peptide 1; Humans; Hypoglycemic Agents; Male; Middle Aged; Natriuretic Peptide, Brain; Plasminogen Activator Inhibitor 1; Triglycerides

Natriuretic peptides (NPs) play a key role in cardiovascular homeostasis, counteracting the deleterious effects of volume and pressure overload and activating antibrotic and antihypertrophic pathways in the heart. N-terminal B-type NP (NT-proBNP) also is a promising biomarker of global cardiovascular risk in the general population, and there is increasing interest on its potential use in diabetic patients for screening of silent cardiovascular abnormalities, cardiovascular risk stratification, and guided intervention. Recently, both atrial NP (ANP) and B-type NP (BNP) have emerged as key mediators in the control of metabolic processes including the heart in the network of organs that regulate energy usage and metabolism. Epidemiological studies have shown that ANP and BNP are reduced in people with obesity, insulin resistance, and diabetes, and this deficiency may contribute to enhance their global cardiovascular risk. Moreover, ANP and BNP have receptors in the adipose tissue, enhance lipolysis and energy expenditure, and modulate adipokine release and food intake. Therefore, low ANP and BNP levels may be not only a consequence but also a cause of obesity, and recent prospective studies have shown that low levels of NT-proBNP and midregional proANP (MR-proANP) are a strong predictor of type 2 diabetes onset. Whether ANP and BNP supplementation may result in either cardiovascular or metabolic benefits in humans remains, however, to be established.

Topics: Adipose Tissue; Animals; Atrial Natriuretic Factor; Biomarkers; Biomedical Research; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Heart; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Risk Factors

Cardiovascular complications, including cardiomegaly, myocardial ischemia and left ventricular hypertrophy, are some of the major determinants of the mortality rate in patients with Cushing's syndrome. We herein report the case of a patient with Cushing's syndrome caused by an adrenal adenoma who presented with congestive heart failure secondary to dilated cardiomyopathy. Follow-up echocardiography showed a marked improvement in the left ventricular cardiac function, and the plasma B-type natriuretic peptide (BNP) levels regressed after successful treatment. "Reversible" dilated cardiomyopathy is rarely associated with Cushing's syndrome; however, it should be recognized. Administering appropriate treatment in a timely manner can reverse this cardiomyopathy along with the other symptoms of Cushing's syndrome.

Topics: Adenoma; Adrenal Cortex Neoplasms; Adrenalectomy; Aged; Biomarkers; Cardiomyopathy, Dilated; Cardiovascular Agents; Circadian Rhythm; Cushing Syndrome; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Heart Failure; Humans; Hydrocortisone; Natriuretic Peptide, Brain; Remission Induction

A recent study reported an association between the brain natriuretic peptide (BNP) promoter T-381C polymorphism (rs198389) and protection against type 2 diabetes (T2D). As replication in several studies is mandatory to confirm genetic results, we analyzed the T-381C polymorphism in seven independent case-control cohorts and in 291 T2D-enriched pedigrees totalling 39 557 subjects of European origin. A meta-analysis of the seven case-control studies (n = 39 040) showed a nominal protective effect [odds ratio (OR) = 0.86 (0.79-0.94), P = 0.0006] of the CC genotype on T2D risk, consistent with the previous study. By combining all available data (n = 49 279), we further confirmed a modest contribution of the BNP T-381C polymorphism for protection against T2D [OR = 0.86 (0.80-0.92), P = 1.4 x 10(-5)]. Potential confounders such as gender, age, obesity status or family history were tested in 4335 T2D and 4179 normoglycemic subjects and they had no influence on T2D risk. This study provides further evidence of a modest contribution of the BNP T-381C polymorphism in protection against T2D and illustrates the difficulty of unambiguously proving modest-sized associations even with large sample sizes.

Topics: Aged; Case-Control Studies; Cohort Studies; Diabetes Mellitus, Type 2; Europe; Genome-Wide Association Study; Genotype; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Pedigree; Polymorphism, Single Nucleotide; Risk Factors; White People

Cardiovascular disease is the leading cause of death among patients with Type 2 diabetes mellitus. The main forms of structural heart disease associated with diabetes are coronary heart disease and diabetic cardiomyopathy, which is characterized by left ventricular hypertrophy, left ventricular diastolic and systolic dysfunction. Asymptomatic structural heart disease is common and associated with a poor prognosis in patients with diabetes. Contemporary practice guidelines do not recommend screening of asymptomatic individuals for structural heart disease. Potential screening modalities, such as echocardiography, are costly and inaccessible. A simple, inexpensive blood test for brain natriuretic peptide is a useful marker of structural heart disease and is a prime candidate for screening patients with Type 2 diabetes mellitus and prioritizing referral for echocardiography.

Topics: Biomarkers; Cardiomyopathies; Diabetes Mellitus, Type 2; Echocardiography; Humans; Hypertrophy, Left Ventricular; Myocardial Ischemia; Natriuretic Peptide, Brain; Ventricular Dysfunction, Left

Brain natriuretic peptide (BNP/NPPB) is a member of the natriuretic family involved in the regulation of blood pressure and blood volume as well as lipolysis control in human fat cells. Thus BNP may play a role in energy metabolism and metabolic diseases. We therefore assessed the association between the BNP promoter T-381C polymorphism and risk of type 2 diabetes and metabolic and BNP expression traits in several population samples. In French population-based samples (n = 3216), we found that individuals bearing the -381CC genotype had lower (P = 0.005) fasting glucose levels than -381TC or -381TT individuals. Moreover, the -381CC genotype was less frequent in individuals with type 2 diabetes (n = 280, 13.6%) or with impaired fasting glucose (n = 248, 12.9%) compared with normoglycaemic individuals (n = 2485, 17.8%). The adjusted odds ratio (OR) (95% CI) of type 2 diabetes for -381CC individuals was 0.69 (0.47-1.00), P = 0.05, when compared with -381T allele bearers. We replicated this association in four additional case-control studies for type 2 diabetes. The overall OR (95% CI) of type 2 diabetes was 0.85 (0.76-0.96), P = 0.008, (under a recessive model) (3593 cases and 6646 controls in total). We also found that the -381C allele was associated with higher plasma BNP concentrations (P = 0.015, n = 634) and higher BNP promoter activity in reporter gene assays. Collectively, these data suggest that relatively high BNP expression may protect against type 2 diabetes in humans.

Topics: Adult; Aged; Animals; Case-Control Studies; Chlorocebus aethiops; COS Cells; Cytosine; Diabetes Mellitus, Type 2; Female; Genetic Predisposition to Disease; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Polymorphism, Single Nucleotide; Risk Factors; Thymine

Topics: Cardiovascular Diseases; Cholesterol; Cholesterol, LDL; Diabetes Mellitus, Type 2; Homocysteine; Humans; Natriuretic Peptide, Brain; Risk Factors; Smoking

Topics: Albuminuria; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Body Weight; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Neuropathies; Diabetic Retinopathy; Diet; Drug Therapy, Combination; Dyslipidemias; Endothelium, Vascular; Glomerular Filtration Rate; Health Behavior; Humans; Hypertension; Insulin Resistance; Kidney; Life Style; Natriuretic Peptide, Brain; Peptide Fragments; Risk Assessment; Risk Factors; Smoking; Smoking Cessation; Survival Analysis; Treatment Outcome; Vitamins

Cardiovascular disease is the most common complication of type 2 diabetes mellitus (type 2 DM), accounting for approximately 80% of deaths. While atherosclerotic vascular disease accounts for much of the cardiovascular morbidity and mortality among diabetic patients, congestive heart failure (CHF) is another key complication associated with diabetes, with an incidence three to five times greater in diabetic patients than in those without diabetes. One of the most promising developments in the treatment of type 2 DM has been the introduction of the thiazolidinedione (TZD) class of drugs, which appear to have pleiotropic effects beyond glycaemic control. Enthusiasm has been tempered, however, by concerns for safety in patients with CHF, given reports of worsening heart failure symptoms and peripheral oedema. With the growing epidemic of type 2 DM and the increasing use of TZDs, such concern has important therapeutic implications for a population of patients with a high prevalence of often subclinical systolic and diastolic dysfunction. This review provides an overview of the currently available data regarding the effects of TZDs on fluid retention and cardiac function. Particular emphasis is placed on the mechanisms of development of peripheral oedema and its significance in patients with impaired left ventricular function. TZDs are well known to cause an expansion in plasma volume; there has also been concern that TZDs may have direct toxic effects on the myocardium, leading to impaired cardiac function. Studies to date do not support this hypothesis and in fact there is growing evidence from animal models and human trials that treatment with TZDs actually improves cardiac function. There are also preclinical data to suggest TZDs may protect the myocardium in the setting of ischaemic insult or the toxic effects of myocardial lipid deposition. Ongoing clinical trials examining the use of these agents in patients at risk for heart failure will probably provide further insight into the aggregate cardiovascular effects of this promising class of medications.

Topics: Animals; Body Fluids; Clinical Trials as Topic; Diabetes Mellitus, Type 2; Edema; Endothelium, Vascular; Heart Failure; Humans; Hypoglycemic Agents; Myocardial Infarction; Myocytes, Cardiac; Natriuretic Peptide, Brain; PPAR gamma; Practice Guidelines as Topic; Thiazolidinediones; Triglycerides; Ventricular Dysfunction, Left

To investigate the effect of left ventricular ejection fraction (LVEF) on the behavior of N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in patients with heart failure and type 2 diabetes mellitus with the use of canagliflozin compared to glimepiride.. Patients (n = 233) from the CANDLE trial were randomly assigned to either the add-on canagliflozin (n = 113) or glimepiride treatment groups (n = 120). The patients were followed-up for 24 weeks. The NT-proBNP levels were measured at baseline and after 24 weeks. The LVEF was determined at baseline.. There was a significant relationship between the baseline NT-proBNP level (X1) and the change in NT-proBNP levels from baseline to 24 weeks (Y) in the canagliflozin group (Y = -0.533 × X1 + 178; r = -0.860, p < 0.001). However, this relationship was not observed in the glimepiride group (p = 0.428). The baseline LVEF (X2) correlated with Y with a marginal significance in the canagliflozin group (Y = 7.72 × X2-549; r = 0.192, p = 0.054), but no relationship was observed in the glimepiride group. In the canagliflozin group, bivariate regression analysis showed a significant correlation between Y, X1, and X2; Y = -0.567 × X1-6.04 × X2 + 542 (R = 0.871, p < 0.001). The partial regression coefficients of X1 (p < 0.001) and X2 (p = 0.006) significantly explained the variance in Y. The correlation coefficient for X2 was negative. There was a significant relationship between the logarithmically transformed NT-proBNP [ln(NT-proBNP)] at baseline (X1') and the change in ln(NT-proBNP) values from baseline to 24 weeks (Y'), a surrogate of the rate of change in NT-proBNP levels, in the canagliflozin group (Y' = -0.18 × X1' + 0.93; r = 0.450, p = 0.001).. The baseline NT-proBNP level significantly affected the extent and the rate of its decrease by canagliflozin. The reduction in NT-proBNP levels by canagliflozin was prominent in patients with a higher LVEF at baseline. However, its confounding effect of LVEF on canagliflozin treatment was not recognized without adjusting for the NT-proBNP level at baseline.

Topics: Biomarkers; Canagliflozin; Diabetes Mellitus, Type 2; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Stroke Volume; Ventricular Function, Left

Pre-heart failure with preserved ejection fraction (pre-HFpEF) is common and has no specific therapy aside from cardiovascular risk factor management.. To investigate the hypothesis that sacubitril/valsartan vs valsartan would reduce left atrial volume index using volumetric cardiac magnetic resonance imaging in patients with pre-HFpEF.. The Personalized Prospective Comparison of ARNI [angiotensin receptor/neprilysin inhibitor] With ARB [angiotensin-receptor blocker] in Patients With Natriuretic Peptide Elevation (PARABLE) trial was a prospective, double-blind, double-dummy, randomized clinical trial carried out over 18 months between April 2015 and June 2021. The study was conducted at a single outpatient cardiology center in Dublin, Ireland. Of 1460 patients in the STOP-HF program or outpatient cardiology clinics, 461 met initial criteria and were approached for inclusion. Of these, 323 were screened and 250 asymptomatic patients 40 years and older with hypertension or diabetes, elevated B-type natriuretic peptide (BNP) greater than 20 pg/mL or N-terminal pro-b-type natriuretic peptide greater than 100 pg/mL, left atrial volume index greater than 28 mL/m2, and preserved ejection fraction greater than 50% were included.. Patients were randomized to angiotensin receptor neprilysin inhibitor sacubitril/valsartan titrated to 200 mg twice daily or matching angiotensin receptor blocker valsartan titrated to 160 mg twice daily.. Maximal left atrial volume index and left ventricular end diastolic volume index, ambulatory pulse pressure, N-terminal pro-BNP, and adverse cardiovascular events.. Among the 250 participants in this study, the median (IQR) age was 72.0 (68.0-77.0) years; 154 participants (61.6%) were men and 96 (38.4%) were women. Most (n = 245 [98.0%]) had hypertension and 60 (24.0%) had type 2 diabetes. Maximal left atrial volume index was increased in patients assigned to receive sacubitril/valsartan (6.9 mL/m2; 95% CI, 0.0 to 13.7) vs valsartan (0.7 mL/m2; 95% CI, -6.3 to 7.7; P < .001) despite reduced markers of filling pressure in both groups. Changes in pulse pressure and N-terminal pro-BNP were lower in the sacubitril/valsartan group (-4.2 mm Hg; 95% CI, -7.2 to -1.21 and -17.7%; 95% CI, -36.9 to 7.4, respectively; P < .001) than the valsartan group (-1.2 mm Hg; 95% CI, -4.1 to 1.7 and 9.4%; 95% CI, -15.6 to 4.9, respectively; P < .001). Major adverse cardiovascular events occurred in 6 patients (4.9%) assigned to sacubitril/valsartan and 17 (13.3%) assigned to receive valsartan (adjusted hazard ratio, 0.38; 95% CI, 0.17 to 0.89; adjusted P = .04).. In this trial of patients with pre-HFpEF, sacubitril/valsartan treatment was associated with a greater increase in left atrial volume index and improved markers of cardiovascular risk compared to valsartan. More work is needed to understand the observed increased cardiac volumes and long-term effects of sacubitril/valsartan in patients with pre-HFpEF.. ClinicalTrials.gov Identifier: NCT04687111.

Topics: Aged; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Diabetes Mellitus, Type 2; Female; Heart Atria; Heart Failure; Humans; Hypertension; Male; Natriuretic Peptide, Brain; Neprilysin; Stroke Volume; Tetrazoles; Valsartan

We carried out a randomized controlled trial using ipragliflozin. We analyzed changes in diastolic function using echocardiography in patients with type 2 diabetes and heart failure with preserved ejection fraction.. We carried out an open-label, multicenter, randomized, two-arm interventional trial. A total of eligible 68 participants were randomly assigned into two groups (ipragliflozin group n = 36; conventional treatment group n = 32). Primary end-points were the change in E/e' and e'. Secondary end-points were other parameters of echocardiography, plasma NT-proBNP level, New York Heart Association class, hemoglobin A1c and blood pressure.. After 24 weeks of follow up, E/e' decreased in both groups (ipragliflozin: 11.0 vs 10.4; conventional treatment 10.5 vs 10.1; multivariate-adjusted P = 0.95). There were no significant differences in the amount of change in E/e', e', echocardiography parameters, plasma NT-proBNP level, New York Heart Association class, hemoglobin A1c and blood pressure between the two groups. In the subgroup analysis, ipragliflozin treatment decreased in left ventricular mass index in patients aged ≥70 years and also decreased in NT-proBNP levels in patients with baseline NT-proBNP ≥400 pg/mL.. In this randomized controlled study carried out in patients with type 2 diabetes and heart failure with preserved ejection fraction, 24-week ipragliflozin treatment did not improve left ventricular diastolic function compared with conventional treatment. As the subgroup, ipragliflozin treatment decreased in left ventricular mass index in participants aged ≥70 years. Geriatr Gerontol Int 2022; 22: 298-304.

Topics: Aged; Diabetes Mellitus, Type 2; Glucosides; Heart Failure; Humans; Natriuretic Peptide, Brain; Stroke Volume; Thiophenes; Ventricular Function, Left

This report describes the baseline clinical profiles and management of DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure) trial participants and how these compare with those in other contemporary heart failure with preserved ejection fraction trials.. The DELIVER trial was designed to evaluate the effects of the sodium-glucose cotransporter-2 inhibitor dapagliflozin on cardiovascular death, heart failure (HF) hospitalization, or urgent HF visits in patients with HF with mildly reduced and preserved left ventricular ejection fraction (LVEF).. Adults with symptomatic HF and LVEF >40%, with or without type 2 diabetes mellitus, elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, and evidence of structural heart disease were randomized to dapagliflozin 10 mg once daily or matching placebo.. DELIVER is the largest and broadest clinical trial of this population to date and enrolled high-risk, well-treated patients with HF with mildly reduced and preserved LVEF. (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure [NCT03619213]).

Topics: Aged; Aged, 80 and over; Atrial Fibrillation; Diabetes Mellitus, Type 2; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Sodium-Glucose Transporter 2 Inhibitors; Stroke Volume; Ventricular Function, Left

The endothelin receptor antagonist atrasentan reduced the risk of kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease (CKD) in the SONAR (Study of Diabetic Nephropathy with Atrasentan) trial, although with a numerically higher incidence of heart failure (HF) hospitalization.. The purpose of this study was to assess if early changes in B-type natriuretic peptide (BNP) and body weight during atrasentan treatment predict HF risk.. Participants with type 2 diabetes and CKD entered an open-label enrichment phase to assess response to atrasentan 0.75 mg/day. Participants without substantial fluid retention (>3 kg body weight increase or BNP increase to >300 pg/mL), were randomized to atrasentan 0.75 mg/day or placebo. Cox proportional hazards regression was used to assess the effects of atrasentan vs placebo on the prespecified safety outcome of HF hospitalizations.. Among 3,668 patients, 73 (4.0%) participants in the atrasentan and 51 (2.8%) in the placebo group developed HF (HR: 1.39; 95% CI: 0.97-1.99; P = 0.072). In a multivariable analysis, HF risk was associated with higher baseline BNP (HR: 2.32; 95% CI: 1.81-2.97) and percent increase in BNP during response enrichment (HR: 1.46; 95% CI: 1.08-1.98). Body weight change was not associated with HF. Exclusion of patients with at least 25% BNP increase during enrichment attenuated the risk of HF with atrasentan (HR: 1.02; 95% CI: 0.66-1.56) while retaining nephroprotective effects (HR: 0.58; 95% CI: 0.44-0.78).. In patients with type 2 diabetes and CKD, baseline BNP and early changes in BNP in response to atrasentan were associated with HF hospitalization, highlighting the importance of natriuretic peptide monitoring upon initiation of atrasentan treatment. (Study Of Diabetic Nephropathy With Atrasentan [SONAR]; NCT01858532).

Topics: Atrasentan; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Double-Blind Method; Endothelin Receptor Antagonists; Endothelins; Heart Failure; Humans; Natriuretic Peptide, Brain; Renal Insufficiency, Chronic; Weight Gain

To use protein biomarkers to identify people with type 2 diabetes at high risk of cardiovascular outcomes and death.. Biobanked serum from 4,957 ELIXA (Evaluation of Lixisenatide in Acute Coronary Syndrome) trial participants was analyzed. Forward-selection Cox models identified independent protein risk factors for major adverse cardiovascular events (MACE) and death that were compared with a previously validated biomarker panel.. NT-proBNP and osteoprotegerin predicted both outcomes. In addition, trefoil factor 3 predicted MACE, and angiopoietin-2 predicted death (C = 0.70 and 0.79, respectively, compared with 0.63 and 0.66 for clinical variables alone). These proteins had all previously been identified and validated. Notably, C statistics for just NT-proBNP plus clinical risk factors were 0.69 and 0.78 for MACE and death, respectively.. NT-proBNP and other proteins independently predict cardiovascular outcomes in people with type 2 diabetes following acute coronary syndrome. Adding other biomarkers only marginally increased NT-proBNP's prognostic value.

Topics: Acute Coronary Syndrome; Biomarkers; Diabetes Mellitus, Type 2; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Risk Assessment; Risk Factors

Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of a deterioration in heart failure (HF) and mortality in patients with a broad range of cardiovascular risks. Recent guidelines recommend considering the use of SGLT2 inhibitors in patients with type 2 diabetes (T2D) and HF, irrespective of their glycemic control status and background use of other glucose-lowering agents including metformin. However, only a small number of studies have investigated whether the effects of SGLT2 inhibitor in these patients differ by the concomitant use of other glucose-lowering agents.. This was a post-hoc analysis of the CANDLE trial (UMIN000017669), an investigator-initiated, multicenter, open-label, randomized, controlled trial. The primary aim of the analysis was to assess the effect of 24 weeks of treatment with canagliflozin, relative to glimepiride, on N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration in patients with T2D and clinically stable chronic HF. In the present analysis, the effect of canagliflozin on NT-proBNP concentration was assessed in the patients according to their baseline use of other glucose-lowering agents.. Almost all patients in the CANDLE trial presented as clinically stable (New York Heart Association class I to II), with about 70% of participants having HF with a preserved ejection fraction phenotype (defined as a left ventricular ejection fraction ≥ 50%) at baseline. Of the 233 patients randomized to either canagliflozin (100 mg daily) or glimepiride (starting dose 0.5 mg daily), 85 (36.5%) had not been taking any glucose-lowering agents at baseline (naïve). Of the 148 patients who had been taking at least one glucose-lowering agent at baseline (non-naïve), 44 (29.7%) and 127 (85.8%) had received metformin or a dipeptidyl dipeptidase-4 (DPP-4) inhibitor, respectively. The group ratio (canagliflozin vs. glimepiride) of proportional changes in the geometric means of NT-proBNP concentration was 0.95 (95% confidence interval [CI] 0.76 to 1.18, p = 0.618) for the naïve subgroup, 0.92 (95% CI 0.79 to1.07, p = 0.288) for the non-naïve subgroup, 0.90 (95% CI 0.68 to 1.20, p = 0.473) for the metformin-user subgroup, and 0.91 (95% CI 0.77 to 1.08, p = 0.271) for the DPP-4 inhibitor-user subgroup. No heterogeneity in the effect of canagliflozin, relative to glimepiride, on NT-proBNP concentration was observed in the non-naïve subgroups compared to that in the naïve subgroup.. The impact of canagliflozin treatment on NT-proBNP concentration appears to be independent of the background use of diabetes therapy in the patient population examined. Trial registration University Medical Information Network Clinical Trial Registry, number 000017669. Registered on May 25, 2015.

Topics: Aged; Biomarkers; Blood Glucose; Canagliflozin; Chronic Disease; Diabetes Mellitus, Type 2; Female; Glycemic Control; Heart Failure; Humans; Japan; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Sodium-Glucose Transporter 2 Inhibitors; Time Factors; Treatment Outcome

Identification of the effective subtypes of treatment for heart failure (HF) is an essential topic for optimizing treatment of the disorder. We hypothesized that the beneficial effect of SGLT2 inhibitors (SGLT2i) on the levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) might depend on baseline diastolic function. To elucidate the effects of SGLT2i in type 2 diabetes mellitus (T2DM) and chronic HF we investigated, as a post-hoc sub-study of the CANDLE trial, the effects of canagliflozin on NT-proBNP levels from baseline to 24 weeks, with the data stratified by left ventricular (LV) diastolic function at baseline.. Patients (n = 233) in the CANDLE trial were assigned randomly to either an add-on canagliflozin (n = 113) or glimepiride treatment groups (n = 120). The primary endpoint was a comparison between the two groups of the changes from baseline to 24 weeks in NT-pro BNP levels, stratified according to baseline ventricular diastolic function.. The change in the geometric mean of NT-proBNP level from baseline to 24 weeks was 0.98 (95% CI 0.89-1.08) in the canagliflozin group and 1.07 (95% CI 0.97-1.18) in the glimepiride group. The ratio of change with canagliflozin/glimepiride was 0.93 (95% CI 0.82-1.05). Responder analyses were used to investigate the response of an improvement in NT-proBNP levels. Although the subgroup analyses for septal annular velocity (SEP-e') showed no marked heterogeneity in treatment effect, the subgroup with an SEP-e' < 4.7 cm/s indicated there was an association with lower NT-proBNP levels in the canagliflozin group compared with that in the glimepiride group (ratio of change with canagliflozin/glimepiride (0.83, 95% CI 0.66-1.04).. In the subgroup with a lower LV diastolic function, canagliflozin showed a trend of reduced NT-pro BNP levels compared to that observed with glimepiride. This study suggests that the beneficial effects of canagliflozin treatment may be different in subgroups classified by the severity of LV diastolic dysfunction.

Topics: Aged; Biomarkers; Blood Glucose; Canagliflozin; Diabetes Mellitus, Type 2; Diastole; Female; Heart Failure; Humans; Japan; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Sodium-Glucose Transporter 2 Inhibitors; Time Factors; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Function, Left

Patients with diabetes who had a recent myocardial infarction (MI) are at high risk of cardiovascular events. Therefore, risk assessment is important for treatment and shared decisions. We used data from EXAMINE trial to investigate whether a multi-proteomic approach would provide specific proteomic signatures and also improve the prognostic capacity for determining the risk of cardiovascular death, MI, stroke, heart failure [HF], all-cause death, and combinations of these outcomes.. 93 circulating proteins (92 from the Olink® CVDII plus troponin) were assessed in 5131 patients. Cox, competing risks, and reclassification measures were applied.. The clinical model showed good discrimination and calibration for all outcomes. On top of the clinical model that included age, sex, smoking, diabetes duration, history of MI (prior to the index MI of inclusion), history of HF hospitalization, history of stroke, atrial fibrillation, hypertension, systolic blood pressure, statin therapy, estimated glomerular filtration rate, and study treatment (alogliptin or placebo), troponin and BNP added prognostic information to the composite of cardiovascular death, MI, or stroke (∆C-index + 5%) and cardiovascular death alone (∆C-index + 7%). Troponin, BNP, and TRAILR2 added prognostic information on all-cause death and the composite of cardiovascular death or HF hospitalization. HF hospitalization alone was improved by adding BNP and Gal-9. For MI, troponin, FGF23, and AMBP added prognostic value; whereas for stroke, only troponin added prognostic value (multi-proteomics improved C-index > 3% [p < 0.001] for all the studied outcomes). The addition of the final biomarker selection to the clinical model improved event reclassification (cNRI from + 23% to + 64%). Specifically, the addition of the biomarkers allowed a better classification of patients at low risk (as having "true" low risk) and patients and high risk (as having "true" high risk). These results were consistent for all the studied outcomes with even more marked differences in the fatal events.. The addition of multi-proteomic biomarkers to a clinical model in this population with diabetes and a recent MI allowed a better risk prediction and event reclassification, potentially helping for better risk assessment and targeted treatment decisions. T2D type 2 diabetes, MI myocardial infarction, CV cardiovascular, HFH heart failure hospitalization, Δ delta, cNRI continuous net reclassification index, BNP brain natriuretic peptide, TRAILR2 trail receptor 2 (or death receptor 5), Gal-9 galectin-9, FGF23 fibroblast growth factor 23.

Topics: Biomarkers; Cause of Death; Comorbidity; Diabetes Mellitus, Type 2; Female; Fibroblast Growth Factor-23; Humans; Hypoglycemic Agents; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Piperidines; Prognosis; Proteomics; Risk Assessment; Survival Rate; Uracil

Dapagliflozin, a sodium-glucose cotransporter-2 inhibitor, reduces cardiovascular death and worsening heart failure in patients with chronic heart failure and reduced ejection fraction. Early initiation during an acute heart failure (AHF) hospitalization may facilitate decongestion, improve natriuresis, and facilitate safe transition to a beneficial outpatient therapy for both diabetes and heart failure.. The objective is to assess the efficacy and safety of initiating dapagliflozin within the first 24 hours of hospitalization in patients with AHF compared to usual care.. The DICTATE-AHF trial will establish the efficacy and safety of early initiation of dapagliflozin during AHF across both AHF and diabetic outcomes in patients with diabetes.

Topics: Acute Disease; Benzhydryl Compounds; Diabetes Mellitus, Type 2; Diabetic Ketoacidosis; Disease Progression; Glucosides; Heart Failure; Hospital Mortality; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Hypotension; Hypovolemia; Insulin; Natriuresis; Natriuretic Peptide, Brain; Patient Readmission; Peptide Fragments; Randomized Controlled Trials as Topic; Renal Insufficiency, Chronic; Sodium Potassium Chloride Symporter Inhibitors; Sodium-Glucose Transporter 2 Inhibitors; Treatment Outcome; Weight Loss

Dapagliflozin reduced the risk of the composite of cardiovascular (CV) death or hospitalization for heart failure (HHF) in patients with type 2 diabetes mellitus in DECLARE-TIMI 58. We hypothesized that baseline N-terminal pro B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin T (hsTnT) levels would help identify patients who are at higher baseline risk and we describe the treatment effects of dapagliflozin in patients according to their baseline NT-proBNP and hsTnT levels.. This was a pre-specified biomarker study from DECLARE-TIMI 58, a randomized, double-blind, placebo-controlled CV outcomes trial of dapagliflozin. Baseline NT-proBNP and hsTnT levels were measured in the TIMI Clinical Trials Laboratory in 14 565 patients. Among the included patients, 9143 patients (62.8%) were male, 1464 (10.1%) had a history of heart failure and the mean age was 63.9 years. The median baseline NT-proBNP and hsTnT levels were 75 pg/mL [interquartile range (IQR) 35-165] and 10.2 pg/mL (IQR 6.9-15.5), respectively. Patients with higher NT-proBNP and hsTnT quartiles had higher rates of CV death/HHF (Q4 vs. Q1: NT-proBNP: 4-year Kaplan-Meier event rates 13.7% vs. 1.0%; hsTnT: 11.8% vs. 1.4%; P-trend <0.001). Dapagliflozin consistently reduced the relative risk of CV death/HHF regardless of baseline NT-proBNP (P-interaction 0.72) or hsTnT quartiles (P-interaction 0.93). Given their higher baseline risk, patients with NT-proBNP and/or hsTnT levels above the median derived larger absolute risk reductions with dapagliflozin (NT-proBNP 1.9% vs. 0%, P-interaction 0.010; hsTnT 1.8% vs. 0.1%, P-interaction 0.026).. Patients with type 2 diabetes mellitus and higher NT-proBNP or hsTnT levels are at increased risk of CV death and HHF. Dapagliflozin reduced the relative risk of CV death/HHF irrespective of NT-proBNP and hsTnT levels, with greater absolute risk reductions seen in patients with higher baseline biomarker levels.

Topics: Biomarkers; Diabetes Mellitus, Type 2; Female; Glucose; Heart Failure; Hospitalization; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Sodium; Sodium-Glucose Transporter 2 Inhibitors; Symporters

A recent large cardiovascular outcome trial in patients with type 2 diabetes (T2DM) demonstrated excess heart failure hospitalization with saxagliptin. We sought to evaluate the impact of saxagliptin on cardiac structure and function using cardiac magnetic resonance imaging (CMR) in patients with T2DM without pre-existing heart failure.. In this prospective study, patients with T2DM without heart failure were prescribed saxagliptin as part of routine guideline-directed management. Clinical assessment, CMR imaging and biomarkers were assessed in a blinded fashion and compared following 6 months of continued treatment. The primary outcome was the change in left ventricular (LV) ejection fraction (LVEF) after 6 months of therapy. Key secondary outcomes included changes in LV and right ventricular (RV) end-diastolic volume, ventricular mass, LV global strain and cardiac biomarkers [N terminal pro B-type natriuretic peptide (NT-proBNP) and high sensitivity C-reactive protein (hsCRP)] over 6 months.. The cohort (n = 16) had a mean age of 59.9 years with 69% being male. The mean hemoglobin A1c (HbA1c) was 8.3%. Mean baseline LVEF was 57% ± 3.4, with no significant change over 6 months (- 0.2%, 95% CI - 2.5, 2.1, p = 0.86). Detailed CMR analyses that included LV/RV volumes, LV mass, and feature tracking-derived strain showed no significant change (all p > 0.50). NT-proBNP and hsCRP levels did not significantly change (p > 0.20).. In this cohort of stable ambulatory patients with T2DM without heart failure, saxagliptin treatment was not associated with adverse ventricular remodeling over 6 months as assessed using CMR and biomarkers.

Topics: Adamantane; Aged; Biomarkers; C-Reactive Protein; Cohort Studies; Diabetes Mellitus, Type 2; Dipeptides; Female; Follow-Up Studies; Heart; Heart Ventricles; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Myocardium; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Stroke Volume; Ventricular Function, Left

Empagliflozin reduces the risk of hospitalization for heart failure in patients with type 2 diabetes and cardiovascular disease. We sought to elucidate the effect of empagliflozin as an add-on therapy on decongestion and renal function in patients with type 2 diabetes admitted for acute decompensated heart failure.. The study was terminated early due to COVID-19 pandemic. We enrolled 59 consecutive patients with type 2 diabetes admitted for acute decompensated heart failure. Patients were randomly assigned to receive either empagliflozin add-on (n=30) or conventional glucose-lowering therapy (n=29). We performed laboratory tests at baseline and 1, 2, 3, and 7 days after randomization. Percent change in plasma volume between admission and subsequent time points was calculated using the Strauss formula.. In this exploratory analysis, empagliflozin achieved effective decongestion without an increased risk of worsening renal function as an add-on therapy in patients with type 2 diabetes with acute decompensated heart failure. Registration: URL: https://www.umin.ac.jp/ctr/index.htm; Unique identifier: UMIN000026315.

Topics: Aged; Aged, 80 and over; Benzhydryl Compounds; Biomarkers; Blood Glucose; COVID-19; Creatinine; Diabetes Mellitus, Type 2; Early Termination of Clinical Trials; Female; Glucosides; Heart Failure; Hospitalization; Humans; Japan; Kidney; Male; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Sodium-Glucose Transporter 2 Inhibitors; Stroke Volume; Time Factors; Treatment Outcome; Ventricular Function, Left

Beyond antihyperglycemic effects, metformin may improve cardiovascular outcomes. Patients with type 2 diabetes often have an elevated plasma level of N-terminal pro B-type as a marker of (sub) clinical cardiovascular disease. We studied whether metformin was associated with a reduction in the serum level of N-terminal pro B-type natriuretic peptide (NT-proBNP) in these patients.. In the HOME trial 390 insulin-treated patients with type 2 diabetes were randomized to 850 mg metformin or placebo three times daily. Plasma samples were drawn at baseline, 4, 17, 30, 43 and 52 months. In a post-hoc analysis we analyzed the change in NT-proBNP in both groups. We used a longitudinal mixed model analysis adjusting for age, sex and prior cardiovascular disease. In a secondary analysis we assessed a possible immediate treatment effect post baseline.. Metformin did not affect NT-proBNP levels over time in the primary analysis (-1% [95%CI -4;3, p = 0.62]). In the secondary analysis there was also no sustained time independent immediate treatment effect (initial increase of 17% [95%CI 4;30, p = 0.006] followed by yearly decrease of -4% [95%CI -7;0, p = 0.07]).. Metformin as compared to placebo did not affect NT-proBNP plasma levels in this 4.3-year placebo-controlled trial. Potential cardioprotective effects of metformin cannot be explained by changes in cardiac pressures or volumes to the extent reflected by NT-proBNP.

Topics: Aged; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Female; Humans; Male; Metformin; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments

Sodium glucose co-transporter 2 inhibitors promote osmotic/natriuretic diuresis and reduce excess fluid volume, and this improves cardiovascular outcomes, including hospitalization for heart failure. We sought to assess the effect of empagliflozin on estimated fluid volumes in patients with type 2 diabetes and cardiovascular disease (CVD).. The study was a post-hoc analysis of the EMBLEM trial (UMIN000024502), an investigator-initiated, multi-center, placebo-controlled, double-blinded, randomized-controlled trial designed primarily to evaluate the effect of 24 weeks of empagliflozin treatment on vascular endothelial function in patients with type 2 diabetes and established CVD. The analysis compared serial changes between empagliflozin (10 mg once daily, n = 52) and placebo (n = 53) in estimated plasma volume (ePV), calculated by the Straus formula and estimated the extracellular volume (eEV), determined by the body surface area, measured at baseline and 4, 12, and 24 weeks after initiation of treatment. Correlations were examined between the changes from baseline to week 24 in each estimated fluid volume parameter and several clinical variables of interest, including N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration.. In an analysis using mixed-effects models for repeated measures, relative to placebo empagliflozin reduced ePV by - 2.23% (95% CI - 5.72 to 1.25) at week 4, - 8.07% (- 12.76 to - 3.37) at week 12, and - 5.60% (- 9.87 to - 1.32) at week 24; eEV by - 70.3 mL (95% CI - 136.8 to - 3.8) at week 4, - 135.9 mL (- 209.6 to - 62.3) at week 12, and - 144.4 mL (- 226.3 to - 62.4) at week 24. The effect of empagliflozin on these parameters was mostly consistent across various patient clinical characteristics. The change in log-transformed NT-proBNP was positively correlated with change in ePV (r = 0.351, p = 0.015), but not with change in eEV.. Our data demonstrated that initiation of empagliflozin treatment substantially reduced estimated fluid volume parameters in patients with type 2 diabetes and CVD, and that this effect was maintained for 24 weeks. Given the early beneficial effect of empagliflozin on cardiovascular outcomes seen in similar patient populations, our findings provide an important insight into the key mechanisms underlying the clinical benefit of the drug. Trial registration University Medical Information Network Clinical Trial Registry, number 000024502.

Topics: Aged; Benzhydryl Compounds; Biomarkers; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Fluid Shifts; Glucosides; Humans; Japan; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Plasma Volume; Sodium-Glucose Transporter 2 Inhibitors; Time Factors; Treatment Outcome; Water-Electrolyte Balance

Metformin is the most widely used oral antihyperglycemic agent for patients with type 2 diabetes mellitus (T2DM). Despite the possible benefits of metformin on diabetes mellitus (DM) and heart failure (HF), acute or unstable HF remains a precaution for its use.. The aim of the present prospective randomized controlled trial was to assess whether metformin treatment has beneficial effects on patients with T2DM with hypertension without overt HF.. A total of 164 patients (92 males, 72 females; median age 66 years) were included in this study. Patients with T2DM with a history of hypertension were randomized 1:1 to treatment for 1 year with either metformin (metformin-treated group) or other hypoglycemic agents (control group). The primary endpoints were changes in brain natriuretic peptide (BNP) levels, left ventricular (LV) mass index, and indicators of LV diastolic function. We also evaluated changes in both clinical findings and blood laboratory examination data.. We observed no significant changes between baseline and 1-year post-treatment in LV mass index, BNP levels, or E/e' (early diastolic transmitral flow velocity/early diastolic mitral annular velocity; an indicator of LV diastolic function) in either the metformin-treated (n = 83) or the control (n = 81) groups. The metformin-treated group had a significant reduction of body mass index (BMI) and low-density lipoprotein cholesterol (LDL-C), but the control group did not. We determined that renal function, including serum creatinine and estimated glomerular filtration rate, deteriorated significantly in the control group but not in the metformin-treated group.. LV mass and diastolic function were not affected after 1 year of metformin treatment in patients with T2DM. However, we observed benefits in terms of reductions in both BMI and LDL-C levels and preservation of renal function.. UMIN000006504. Registered 7 October 2011.

Topics: Aged; Body Mass Index; Cholesterol, LDL; Diabetes Mellitus, Type 2; Female; Heart Ventricles; Humans; Hypertension; Hypoglycemic Agents; Male; Metformin; Natriuretic Peptide, Brain; Organ Size; Treatment Outcome; Ventricular Function, Left

Sodium glucose cotransporter 2 (SGLT2) inhibitors are established antidiabetic drugs with proven cardiovascular benefit. Although growing evidence suggests beneficial effects on myocardial remodeling, fluid balance and cardiac function, the impact of empagliflozin initiated early after acute myocardial infarction (AMI) has not been investigated yet. Therefore, the impact of EMpagliflozin on cardiac function and biomarkers of heart failure in patients with acute MYocardial infarction (EMMY) trial was designed to investigate the efficacy and safety of empagliflozin in diabetic and non-diabetic patients after severe AMI.. Within a multicenter, randomized, double-blind, placebo-controlled, phase 3b trial we will enroll patients with AMI and characteristics suggestive of severe myocardial necrosis are randomized in a 1:1 ratio to empagliflozin (10 mg once daily) or matching placebo. The primary endpoint is the impact of empagliflozin on changes in NT-proBNP within 6 months after AMI. Secondary endpoints include changes in echocardiographic parameters, levels of ketone body concentrations, HbA1c levels and body weight, respectively. Hospitalization rate due to heart failure or other causes, the duration of hospital stay and all-cause mortality will be assessed as exploratory secondary endpoints.. The EMMY trial will test empagliflozin in patients with AMI regardless of their diabetic status. The EMMY trial may therefore underpin the concept of SGLT2 inhibition to improve cardiac remodeling, pre-and afterload reduction and cardiac metabolism regardless of its antidiabetic effects. Results will provide the rationale for the conduct of a cardiovascular outcome trial to test the effect of empagliflozin in patients with AMI.

Topics: Benzhydryl Compounds; Diabetes Mellitus, Type 2; Double-Blind Method; Echocardiography; Glucosides; Glycated Hemoglobin; Heart Failure; Hospitalization; Humans; Ketone Bodies; Length of Stay; Mortality; Myocardial Infarction; Natriuretic Peptide, Brain; Peptide Fragments; Sodium-Glucose Transporter 2 Inhibitors

Topics: Acute Coronary Syndrome; Aged; Biomarkers; Blood Proteins; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Double-Blind Method; Female; Galectin 3; Galectins; Growth Differentiation Factor 15; Heart Disease Risk Factors; Heart Failure; Hospitalization; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Piperidines; Prognosis; Risk Assessment; Troponin I; Uracil

Asymptomatic patients with coronary artery disease (CAD), hypertension and/or type 2 diabetes mellitus (T2DM) are at greater risk of developing heart failure (HF). Fibrosis, leading to myocardial and vascular dysfunction, might be an important pathway of progression. The Heart OMics in AGing (HOMAGE) trial aims to investigate the effects of spironolactone on serum markers of collagen metabolism and on cardiovascular structure and function in people at risk of developing HF and potential interactions with a marker of fibrogenic activity, galectin-3.. The HOMAGE trial will provide insights on the effect of spironolactone on pathways that might drive progression to HF.. ClinicalTrials.gov NCT02556450.

Topics: Aged; Aging; Biomarkers; Diabetes Mellitus, Type 2; Female; Fibrosis; Heart Failure; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Spironolactone; Stroke Volume; Ventricular Function, Left

Little is known about the impact of sodium glucose co-transporter 2 (SGLT2) inhibitors on cardiac biomarkers, such as natriuretic peptides, in type 2 diabetes (T2D) patients with concomitant chronic heart failure (CHF). We compared the effect of canagliflozin with glimepiride, based on changes in N-terminal pro-brain natriuretic peptide (NT-proBNP), in that patient population.. Patients with T2D and stable CHF, randomized to receive canagliflozin 100 mg or glimepiride (starting-dose: 0.5 mg), were examined using the primary endpoint of non-inferiority of canagliflozin vs. glimepiride, defined as a margin of 1.1 in the upper limit of the two-sided 95% confidence interval (CI) for the group ratio of percentage change in NT-proBNP at 24 weeks. Data analysis of 233 patients showed mean left ventricular ejection fraction (LVEF) at randomization was 57.6 ± 14.6%, with 71% of patients having a preserved LVEF (≥50%). Ratio of NT-proBNP percentage change was 0.48 (95% CI, -0.13 to 1.59, P = 0.226) and therefore did not meet the prespecified non-inferiority margin. However, NT-proBNP levels did show a non-significant trend lower in the canagliflozin group [adjusted group difference; -74.7 pg/mL (95% CI, -159.3 to 10.9), P = 0.087] and also in the subgroup with preserved LVEF [-58.3 (95% CI, -127.6 to 11.0, P = 0.098]).. This study did not meet the predefined primary endpoint of changes in NT-proBNP levels, with 24 weeks of treatment with canagliflozin vs. glimepiride. Further research is warranted to determine whether patients with heart failure with preserved ejection fraction, regardless of diabetes status, could potentially benefit from treatment with SGLT2 inhibitors.

Topics: Canagliflozin; Diabetes Mellitus, Type 2; Heart Failure; Humans; Natriuretic Peptide, Brain; Stroke Volume; Ventricular Function, Left

To assess the effect of liraglutide, a glucagon-like peptide-1 receptor agonist, on urinary sodium excretion as well as on circulating adrenomedullin and copeptin levels in patients with type 2 diabetes (T2D).. In the LIVE study, patients (n = 241) with left ventricular ejection fraction ≤45% were randomized to liraglutide 1.8 mg daily or placebo for 24 weeks, and 30% had a concomitant diagnosis of T2D. Plasma levels of N-terminal brain-natriuretic-peptide (NT-proBNP) (a predefined secondary endpoint), midregional pro-atrial-natriuretic-peptide (MR-proANP), midregional pro-adrenomedullin (MR-proADM) and copeptin were measured at baseline and after 24 weeks in this substudy. The potential effect modification of T2D was assessed.. In the eligible subgroup of 231 patients with available biomarkers (115 randomized to liraglutide and 116 to placebo), MR-proANP decreased by 12% (P = .002) and NT-proBNP by 9% (P = .009) during liraglutide treatment compared with placebo at week 24. Interaction with T2D for the treatment effect of change in MR-proANP and NT-proBNP levels was P = .003 and P = .03, respectively. Consequently, in patients with T2D, liraglutide decreased MR-proANP by 27% (P < .001) and NT-proBNP by 25% (P = .02) compared with placebo, whereas no change was observed in patients without T2D. There was no effect of liraglutide on MR-proADM (P = .10) or copeptin (P = .52).. Liraglutide decreased the A- and B-type natriuretic peptides significantly in patients with heart failure with reduced ejection fraction (HFrEF) and concomitant T2D, suggesting a beneficial mechanism of liraglutide in T2D patients with HFrEF.

Topics: Atrial Natriuretic Factor; Biomarkers; Diabetes Mellitus, Type 2; Glucagon-Like Peptide-1 Receptor; Heart Failure; Humans; Liraglutide; Natriuretic Peptide, Brain; Peptide Fragments; Stroke Volume; Ventricular Function, Left

Topics: Aged; Biomarkers; Diabetes Mellitus, Type 2; Drug Administration Schedule; Female; Heart Failure; Humans; Hypoglycemic Agents; Inositol; Male; Middle Aged; Natriuretic Peptide, Brain; Prospective Studies; Sodium-Glucose Transporter 2 Inhibitors; Sorbitol; Stroke Volume

The aim of this study was to determine the levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) after treatment with sodium-glucose cotransporter-2 (SGLT2) inhibitor or dipeptidyl peptidase-4 (DPP4) inhibitor in patients with type-2 diabetes inadequately controlled by insulin, and to determine whether variation in ANP levels can explain favorable cardiovascular outcome.. We enrolled 56 patients, aged 18-80years, with type-2 diabetes inadequately controlled by insulin: i.e., HbA1c level 7.5-10.5% despite at least 8weeks' injectable insulin at a stable mean dose of 20-150IU daily, with or without no more than two oral antidiabetic agents.. The 56 patients were randomized between 3 treatment groups: SGLT2 inhibitor (n=18), DPP4 inhibitor (n=19) and placebo (n=19). Patients who received SGLT2 inhibitor or DPP4 inhibitor treatment all showed significantly lower HbA1c levels, fasting blood glucose (FBG) levels and systolic blood pressure at 24weeks than controls. SGLT2 inhibitor treatment decreased ANP levels, BNP levels, systolic blood pressure and weight compared with placebo. Compared to those receiving DPP4 inhibitor, patients receiving SGLT2 inhibitor showed lower HbA1c levels (7.01 vs. 7.58%; P=0.03), ANP levels (28.41 vs. 43.03 pg/mL; P=0.00) and weight (66.14 vs. 71.76 kg; P=0.04) at 24weeks after adjusting for baseline values. The SGLT2 inhibitor group showed higher sodium concentrations than the placebo and DPP4 inhibitor groups (145.89 vs. 143.89 and 144.79 mmol/L, respectively; P=0.00 and P=0.04) at 24 weeks. ANP and BNP levels did not significantly correlate with HbA1c and blood glucose levels.. These results indicated that SGLT2 inhibitors may be superior to DPP4 inhibitors in reducing risk of cardiovascular disease in diabetic patients. The major study limitation was the small number of patients per group, which should be enlarged in further research.

Topics: Adamantane; Adolescent; Adult; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Benzhydryl Compounds; Blood Glucose; Diabetes Mellitus, Type 2; Dipeptides; Female; Glucosides; Glycated Hemoglobin; Humans; Insulin; Male; Middle Aged; Natriuretic Peptide, Brain; Sodium-Glucose Transporter 2 Inhibitors; Treatment Outcome; Young Adult

Topics: Aged; Amides; Antihypertensive Agents; Cardiovascular Diseases; Diabetes Complications; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Fumarates; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Risk Assessment

Canagliflozin reduces cardiovascular events including hospitalization for heart failure (HHF) in patients with type 2 diabetes and cardiovascular risk. Elevated amino-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations are associated with HF diagnosis and predict cardiovascular risk.. The purpose of this study was to measure NT-proBNP in CANVAS (Canagliflozin Cardiovascular Assessment Study) participants.. Associations between baseline NT-proBNP and cardiovascular, renal, and mortality outcomes and intervention-associated changes were determined.. Of the 4,330 participants in the CANVAS trial, NT-proBNP was measured in 3,587, 2,918, and 995 participants at baseline, 1 year, and 6 years, respectively. The median baseline NT-proBNP concentration was 91 pg/ml, and 39.3% had NT-proBNP ≥125 pg/ml. NT-proBNP was higher in those with investigator-reported HF (13% of participants at baseline) versus those without (187 pg/ml vs. 81 pg/ml), with substantial overlap between groups. By 1 year, NT-proBNP increased with placebo, whereas canagliflozin reduced NT-proBNP by 11% (geometric mean ratio for canagliflozin vs. placebo = 0.89 [95% confidence interval (CI): 0.84 to 0.94]; p < 0.001). Lower NT-proBNP with canagliflozin was also observed at 6 years (p = 0.004). In adjusted models, baseline NT-proBNP ≥125 pg/ml was prognostic for incident HHF (hazard ratio [HR]: 5.40; 95% CI: 2.67 to 10.9), HHF/cardiovascular death (HR: 3.52; 95% CI: 2.38 to 5.20), and all-cause death (HR: 2.53; 95% CI: 1.78 to 3.61). Mediation analyses suggested that 10.4% of the effects of canagliflozin on HHF were reflected in NT-proBNP lowering.. A substantial percentage of patients in the CANVAS trial had elevated NT-proBNP values. Canagliflozin reduced NT-proBNP concentrations versus placebo; however, reduction in NT-proBNP explained only a small proportion of the benefit of canagliflozin on HF events. (CANVAS [CANagliflozin cardioVascular Assessment Study]; NCT01032629).

Topics: Aged; Biomarkers; Canagliflozin; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Female; Heart Disease Risk Factors; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Risk Reduction Behavior; Sodium-Glucose Transporter 2 Inhibitors; Treatment Outcome

EMPEROR-Preserved is an ongoing trial evaluating the effect of empagliflozin in patients with heart failure with preserved ejection fraction (HFpEF). This report describes the baseline characteristics of the EMPEROR-Preserved cohort and compares them with patients enrolled in prior HFpEF trials.. EMPEROR-Preserved is a phase III randomized, international, double-blind, parallel-group, placebo-controlled trial in which 5988 symptomatic HFpEF patients [left ventricular ejection fraction (LVEF) >40%] with and without type 2 diabetes mellitus (T2DM) have been enrolled. Patients were required to have elevated N-terminal pro B-type natriuretic peptide (NT-proBNP) concentrations (i.e. >300 pg/mL in patients without and >900 pg/mL in patients with atrial fibrillation) along with evidence of structural changes in the heart or documented history of heart failure hospitalization. Among patients enrolled from various regions (45% Europe, 11% Asia, 25% Latin America, 12% North America), the mean age was 72 ± 9 years, 45% were women. Almost all patients had New York Heart Association class II or III symptoms (99.6%), and 23% had prior heart failure hospitalization within 12 months. Thirty-three percent of the patients had baseline LVEF of 41-50%. The mean LVEF (54 ± 9%) was slightly lower while the median NT-proBNP [974 (499-1731) pg/mL] was higher compared with previous HFpEF trials. Presence of comorbidities such as diabetes (49%) and chronic kidney disease (50%) were common. The majority of the patients were on angiotensin-converting enzyme inhibitors/angiotensin receptor blockers/angiotensin receptor-neprilysin inhibitors (80%) and beta-blockers (86%), and 37% of patients were on mineralocorticoid receptor antagonists.. When compared with prior trials in HFpEF, the EMPEROR-Preserved cohort has a somewhat higher burden of comorbidities, lower LVEF, higher median NT-proBNP and greater use of mineralocorticoid receptor antagonists at baseline. Results of the EMPEROR-Preserved trial will be available in 2021.

Topics: Aged; Aged, 80 and over; Benzhydryl Compounds; Biomarkers; Cardiovascular Agents; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Glucosides; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Sodium-Glucose Transporter 2 Inhibitors; Stroke Volume

We examined the prognostic importance of N-terminal pro B-type natriuretic peptide (NT-proBNP) and troponin T (TnT) in heart failure patients with and without diabetes.. We measured NT-proBNP and TnT in the biomarker substudy of the Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure trial (PARADIGM-HF). Of 1907 patients, 759 (40%) had diabetes. Median TnT in patients with diabetes was 18 (interquartile range 11-27) ng/L and 13 (9-21) ng/L in those without (P < 0.001). The TnT frequency-distribution curve was shifted to the right in patients with diabetes, compared to those without diabetes. By contrast, NT-proBNP did not differ between patients with and without diabetes. Diabetes and each biomarker were predictive of worse outcomes. Thus, patients with diabetes, an elevated TnT and a NT-proBNP level in the highest tertile (9% of all patients) had an absolute risk of cardiovascular death or heart failure hospitalization of 265 per 1000 person-years, compared to a rate of 42 per 1000 person-years in those without diabetes, a TnT < 18 ng/L and a NT-proBNP in the lowest tertile (16% of all patients). TnT remained an independent predictor of adverse outcomes in multivariable analyses including NT-proBNP.. TnT is elevated to a greater extent in heart failure patients with diabetes compared to those without (whereas NT-proBNP is not). TnT and NT-proBNP are additive in predicting risk and when combined help identify diabetes patients at extremely high absolute risk.

Topics: Aged; Biomarkers; Diabetes Mellitus, Type 2; Europe; Female; Heart Failure; Humans; Male; Morbidity; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Prospective Studies; Risk Factors; Stroke Volume; Survival Rate; Troponin T

Sodium-glucose co-transporter 2 (SGLT2) inhibitors have been shown to reduce the risk of incident heart failure hospitalization in individuals with type 2 diabetes who have, or are at high risk of, cardiovascular disease. Most patients in these trials did not have heart failure at baseline and the effect of SGLT2 inhibitors on outcomes in individuals with established heart failure (with or without diabetes) is unknown.. The Dapagliflozin And Prevention of Adverse-outcomes in Heart Failure trial (DAPA-HF) is an international, multicentre, parallel group, randomized, double-blind, study in patients with chronic heart failure, evaluating the effect of dapagliflozin 10 mg, compared with placebo, given once daily, in addition to standard care, on the primary composite outcome of a worsening heart failure event (hospitalization or equivalent event, i.e. an urgent heart failure visit) or cardiovascular death. Patients with and without diabetes are eligible and must have a left ventricular ejection fraction ≤ 40%, a moderately elevated N-terminal pro B-type natriuretic peptide level, and an estimated glomerular filtration rate ≥ 30 mL/min/1.73 m. DAPA-HF will determine the efficacy and safety of the SGLT2 inhibitor dapagliflozin, added to conventional therapy, in a broad spectrum of patients with heart failure and reduced ejection fraction.

Topics: Benzhydryl Compounds; Cardiovascular Diseases; Chronic Disease; Diabetes Mellitus, Type 2; Double-Blind Method; Glucosides; Heart Failure; Hospitalization; Humans; Natriuretic Peptide, Brain; Patient Reported Outcome Measures; Peptide Fragments; Sodium-Glucose Transporter 2 Inhibitors; Stroke Volume

Reports that sodium glucose cotransporter 2 inhibitors decrease cardiovascular death and events in patients with diabetes have attracted attention in the cardiology field. We conducted a study of canagliflozin in patients with chronic heart failure and type II diabetes.. Thirty-five Japanese patients with chronic heart failure and type II diabetes were treated with canagliflozin for 12 months. The primary endpoints were the changes of subcutaneous, visceral, and total fat areas at 12 months determined by computed tomography. Secondary endpoints included markers of glycemic control, renal function, and oxidative stress, as well as lipid parameters, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), flow-mediated dilation (FMD), and echocardiographic left ventricular function.. All fat areas (subcutaneous, visceral, and total) showed a significant decrease at 12 months. ANP and BNP also decreased significantly, along with improvement of renal function, oxidized LDL, and E/e', FMD increased significantly after canagliflozin treatment.. Canagliflozin demonstrated cardiac and renal protective effects as well as improving oxidative stress, diastolic function, and endothelial function. This drug was effective in patients who had heart failure with preserved ejection fraction and could become first-line therapy for such patients with diabetes. Trial registration UMIN ( http://www.umin.ac.jp/ ), Study ID: UMIN000021239.

Topics: Adiposity; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Biomarkers; Blood Glucose; Canagliflozin; Chronic Disease; Diabetes Mellitus, Type 2; Female; Heart; Heart Failure; Humans; Japan; Kidney; Male; Middle Aged; Natriuretic Peptide, Brain; Prospective Studies; Sodium-Glucose Transporter 2 Inhibitors; Time Factors; Treatment Outcome; Weight Loss

Data from recent cardiovascular outcome trials in patients with type 2 diabetes (T2D) suggest that sodium-glucose cotransporter 2 (SGLT2) inhibitors can prevent development of heart failure (HF) and prolong life in patients without HF. Ongoing event-driven trials are investigating whether the same effect is present in patients with well-defined HF. The mechanism behind the effect of SGLT2 inhibitors in patients with T2D and the potential effect in patients with overt HF is presently unknown.. This is a randomized, double-blinded, placebo-controlled, parallel group, clinical trial including HF patients with reduced left ventricular ejection fraction (HFrEF) with an ejection fraction ≤ 40% on optimal therapy recruited from specialized HF clinics in Denmark. The primary aim is to investigate the effect of the SGLT2 inhibitor empagliflozin on N-terminal pro-brain natriuretic peptide (NT-proBNP). Secondary endpoints include cardiac biomarkers, function and hemodynamics, metabolic and renal parameters, daily activity level, and quality of life. Patients are assigned 1:1 to 90 days treatment with empagliflozin 10 mg daily or placebo. Patients with T2D are required to be on recommended doses of anti-glycemic therapy with a hemoglobin A1c (HbA1c) of 6.5-10.0% (48-86 mmol/mol). To show a between-group difference in the change of NT-proBNP of 30%, a total of 189 patients will be included.. The Empire HF trial will elucidate the effects and modes of action of empagliflozin in HFrEF patients with and without T2D and provide important mechanistic data which will complement ongoing event-driven trials.. Clinicaltrialsregister.eu, EudraCT Number 2017-001341-27 . Registered on 29 May 2017. ClinicalTrials.gov, NCT03198585 . Registered on 26 June 2017.

Topics: Benzhydryl Compounds; Diabetes Mellitus, Type 2; Double-Blind Method; Glucosides; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Quality of Life; Sodium-Glucose Transporter 2 Inhibitors; Stroke Volume

To define the predictors of long-term mortality in patients with type 2 diabetes mellitus and recent acute coronary syndrome.. A total of 7226 patients from a randomized trial, testing the effect on cardiovascular outcomes of the dual peroxisome proliferator-activated receptor agonist aleglitazar in patients with type 2 diabetes mellitus and recent acute coronary syndrome (AleCardio trial), were analysed. Median follow-up was 2 years. The independent mortality predictors were defined using Cox regression analysis. The predictive information provided by each variable was calculated as percent of total chi-square of the model. All-cause mortality was 4.0%, with cardiovascular death contributing for 73% of mortality. The mortality prediction model included N-terminal proB-type natriuretic peptide (adjusted hazard ratio = 1.68; 95% confidence interval = 1.51-1.88; 27% of prediction), lack of coronary revascularization (hazard ratio = 2.28; 95% confidence interval = 1.77-2.93; 18% of prediction), age (hazard ratio = 1.04; 95% confidence interval = 1.02-1.05; 15% of prediction), heart rate (hazard ratio = 1.02; 95% confidence interval = 1.01-1.03; 10% of prediction), glycated haemoglobin (hazard ratio = 1.11; 95% confidence interval = 1.03-1.19; 8% of prediction), haemoglobin (hazard ratio = 1.01; 95% confidence interval = 1.00-1.02; 8% of prediction), prior coronary artery bypass (hazard ratio = 1.61; 95% confidence interval = 1.11-2.32; 7% of prediction) and prior myocardial infarction (hazard ratio = 1.40; 95% confidence interval = 1.05-1.87; 6% of prediction).. In patients with type 2 diabetes mellitus and recent acute coronary syndrome, mortality prediction is largely dominated by markers of cardiac, rather than metabolic, dysfunction.

Topics: Acute Coronary Syndrome; Aged; Biomarkers; Blood Glucose; Chi-Square Distribution; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Kaplan-Meier Estimate; Male; Middle Aged; Multivariate Analysis; Myocardial Revascularization; Natriuretic Peptide, Brain; Oxazoles; Peptide Fragments; Predictive Value of Tests; Proportional Hazards Models; Risk Assessment; Risk Factors; Thiophenes; Time Factors; Treatment Outcome

Incretin-based therapies are used in the treatment of type 2 diabetes mellitus (T2DM) and obesity. We investigated the changes in arterial stiffness and left ventricular (LV) myocardial deformation after 6-month treatment with the GLP-1 analogue liraglutide in subjects with newly diagnosed T2DM.. We randomized 60 patients with newly diagnosed and treatment-naive T2DM to receive either liraglutide (n = 30) or metformin (n = 30) for 6 months. We measured at baseline and after 6-month treatment: (a) carotid-femoral pulse wave velocity (PWV) (b) LV longitudinal strain (GLS), and strain rate (GLSR), peak twisting (pTw), peak twisting velocity (pTwVel) and peak untwisting velocity (pUtwVel) using speckle tracking echocardiography. LV untwisting was calculated as the percentage difference between peak twisting and untwisting at MVO (%dpTw-Utw. After 6-months treatment, subjects that received liraglutide presented with a reduced PWV (11.8 ± 2.5 vs. 10.3 ± 3.3 m/s), MDA (0.92 [0.45-2.45] vs. 0.68 [0.43-2.08] nM/L) and NT-proBNP (p < 0.05) in parallel with an increase in GLS (- 15.4 ± 3 vs. - 16.6 ± 2.7), GLSR (0.77 ± 0.2 vs. 0.89 ± 0.2), pUtwVel (- 97 ± 49 vs. - 112 ± 52°, p < 0.05), %dpTw-Utw. Six-month treatment with liraglutide improves arterial stiffness, LV myocardial strain, LV twisting and untwisting and NT-proBNP by reducing oxidative stress in subjects with newly diagnosed T2DM. ClinicalTrials.gov Identifier NCT03010683.

Topics: Adult; Biomarkers; Biomechanical Phenomena; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Cardiomyopathies; Female; Glucagon-Like Peptide-1 Receptor; Greece; Humans; Hypoglycemic Agents; Incretins; Liraglutide; Male; Middle Aged; Myocardial Contraction; Natriuretic Peptide, Brain; Oxidative Stress; Peptide Fragments; Time Factors; Treatment Outcome; Vascular Stiffness; Ventricular Function, Left

Insulin resistance has been linked to development and progression of atherosclerosis and is present in most patients with type 2 diabetes. Whether the degree of insulin resistance predicts adverse outcomes in patients with type 2 diabetes and acute coronary syndrome (ACS) is uncertain.. The Effect of Aleglitazar on Cardiovascular Outcomes after Acute Coronary Syndrome in Patients with Type 2 Diabetes Mellitus trial compared the peroxisome proliferator-activated receptor-α/γ agonist aleglitazar with placebo in patients with type 2 diabetes and recent ACS. In participants not treated with insulin, we determined whether baseline homeostasis model assessment of insulin resistance (HOMA-IR; n = 4303) or the change in HOMA-IR on assigned study treatment (n = 3568) was related to the risk of death or major adverse cardiovascular events (cardiovascular death, myocardial infarction, and stroke) in unadjusted and adjusted models. Because an inverse association of HOMA-IR with N-terminal pro-B-type natriuretic peptide (NT-proBNP) has been described, we specifically examined effects of adjustment for the latter.. In unadjusted analysis, twofold higher baseline HOMA-IR was associated with lower risk of death [hazard ratio (HR): 0.79, 95% CI: 0.68 to 0.91, P = 0.002]. Adjustment for 24 standard demographic and clinical variables had minimal effect on this association. However, after further adjustment for NT-proBNP, the association of HOMA-IR with death was no longer present (adjusted HR: 0.99, 95% CI: 0.83 to 1.19, P = 0.94). Baseline HOMA-IR was not associated with major adverse cardiovascular events, nor was the change in HOMA-IR on study treatment associated with death or major adverse cardiovascular events.. After accounting for levels of NT-proBNP, insulin resistance assessed by HOMA-IR is not related to the risk of death or major adverse cardiovascular events in patients with type 2 diabetes and ACS.

Topics: Acute Coronary Syndrome; Aged; Diabetes Mellitus, Type 2; Female; Homeostasis; Humans; Hypoglycemic Agents; Insulin; Insulin Resistance; Male; Middle Aged; Natriuretic Peptide, Brain; Oxazoles; Peptide Fragments; Proportional Hazards Models; Risk Assessment; Risk Factors; Survival Analysis; Thiophenes

The aim of the study was to examine the relationship between the brain natriuretic peptide (BNP) level and prognosis of diabetic nephropathy. The subjects were 100 Japanese outpatients with type 2 diabetes mellitus with microalbuminuria. Associations between metabolic parameters at baseline, including BNP, and prognosis of diabetic nephropathy (progression of diabetic nephropathy, cardiovascular events, and death) were examined for 7 years. In Cox proportional hazard analysis, HbA1c, albumin-creatinine ratio (ACR) and BNP were identified as significant factors for progression of diabetic nephropathy (p=0.033, p=0.037, and p=0.044, respectively), BNP was identified as significant factor for cardiovascular events (p=0.046), and estimated glomerular filtration rate (eGFR) and BNP were identified as significant factors for death (p=0.046 and p=0.048, respectively). In Kaplan-Meier analysis, risks of progression of diabetic nephropathy, cardiovascular events, and death were significantly different between patients with a low and a high BNP level (p=0.046, p=0.002, and p=0.025, respectively). ROC curve analysis gave cutoff values for BNP of 14.9 pg/ml for progression of diabetic nephropathy, 16.3 pg/ml for cardiovascular events, and 17.6 pg/ml for death (p=0.047, p=0.035, p=0.018, respectively). In conclusion, the BNP level is associated with prognosis in diabetic nephropathy.

Topics: Aged; Albuminuria; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Disease-Free Survival; Female; Follow-Up Studies; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Survival Rate

Sodium retention and volume overload are the main determinants of poor response to renin-angiotensin-aldosterone system (RAAS) inhibition in patients with diabetes. As volume excess can exist without symptoms, biomarkers are needed to identify a priori which patients are volume overloaded and may experience less benefit from RAAS inhibition. N-terminal pro-brain natriuretic peptide (NT-proBNP) is released in the setting of increased cardiac wall stress and volume overload. We conducted a post hoc analysis among 5081 patients with type 2 diabetes mellitus participating in the ALTITUDE trial to investigate whether NTproBNP can predict the effects of additional therapy with aliskiren on cardio-renal endpoints. Aliskiren compared to placebo reduced the risk of the primary cardio-renal endpoint events by 20% (95% confidence interval [CI] 16 to 61) and 2% (95% CI -42 to 30) in the two lowest NT-proBNP tertiles, and it increased the risk by 25% (95% CI -4 to 96) in the highest NT-proBNP tertile (P value for trend = 0.009). Similar trends were observed for the cardiovascular and end-stage renal disease endpoints. Effects of aliskiren compared to placebo on safety outcomes (hyperkalaemia and hospitalization for acute kidney injury) were independent of NT-proBNP. In conclusion, baseline NT-proBNP may be used as a marker to predict the response to aliskiren with regard to cardio-renal outcomes when added to standard therapy with RAAS inhibition.

Topics: Aged; Amides; Antihypertensive Agents; Biomarkers; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Double-Blind Method; Drug Therapy, Combination; Female; Fumarates; Humans; Hypoglycemic Agents; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Renin-Angiotensin System; Risk Factors; Treatment Outcome

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have beneficial effects on several cardiometabolic biomarkers, but this is not sufficient to fully explain the significant reduction in cardiovascular risk and mortality reported with SGLT2 inhibitor treatment in patients with diabetes mellitus. The 8-week, randomized, open-label SHIFT-J study investigated the effects of adding canagliflozin vs intensified antihyperglycemic therapy on nocturnal home blood pressure (BP) in patients with poorly controlled type 2 diabetes and nocturnal BP on existing therapy. Patients were randomized to oral canagliflozin 100 mg/d or control (increased hypoglycemic dosage/addition of another hypoglycemic agent). The efficacy analysis included 78 patients (mean 69 years; 59% male). Nocturnal home systolic BP [HSBP] decreased by 5.23 mm Hg in the canagliflozin group and by 1.04 mm Hg in the control group (P = 0.078 for between-group difference in change from baseline to week 8 [primary endpoint]); corresponding decreases in HSBP from baseline to week 4 were 5.08 and 1.38 mm Hg, respectively (P = 0.054). Reductions in morning HSBP from baseline to week 4 (-6.82 mm Hg vs -1.26 mm Hg, P = 0.038) and evening HSBP from baseline to week 8 (-8.74 mm Hg vs -2.36 mm Hg, P = 0.012) were greater in the canagliflozin group than in the control group. Body mass index (P < 0.001) and N-terminal pro B-type natriuretic peptide level (NT-proBNP; P = 0.023) decreased more in the canagliflozin group than in the control group. Glycemic control improved comparably in both groups. Reduction of HSBP and NT-proBNP level may be potential mechanism by which SGLT2 inhibitors reduce cardiovascular event risk.

Topics: Aged; Blood Pressure; Blood Pressure Determination; Canagliflozin; Cardiovascular Diseases; Circadian Rhythm; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Japan; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Sodium-Glucose Transporter 2 Inhibitors

Natriuretic peptides are recognized as important predictors of cardiovascular events in patients with heart failure, but less is known about their prognostic importance in patients with acute coronary syndrome. We sought to determine whether B-type natriuretic peptide (BNP) and N-terminal prohormone B-type natriuretic peptide (NT-proBNP) could enhance risk prediction of a broad range of cardiovascular outcomes in patients with acute coronary syndrome and type 2 diabetes mellitus.. Patients with a recent acute coronary syndrome and type 2 diabetes mellitus were prospectively enrolled in the ELIXA trial (n=5525, follow-up time 26 months). Best risk models were constructed from relevant baseline variables with and without BNP/NT-proBNP. C statistics, Net Reclassification Index, and Integrated Discrimination Index were analyzed to estimate the value of adding BNP or NT-proBNP to best risk models. Overall, BNP and NT-proBNP were the most important predictors of all outcomes examined, irrespective of history of heart failure or any prior cardiovascular disease. BNP significantly improved C statistics when added to risk models for each outcome examined, the strongest increments being in death (0.77-0.82,. In patients with a recent acute coronary syndrome and type 2 diabetes mellitus, BNP and NT-proBNP were powerful predictors of cardiovascular outcomes beyond heart failure and death, ie, were also predictive of MI and stroke. Natriuretic peptides added as much predictive information about death as all other conventional variables combined.. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01147250.

Topics: Acute Coronary Syndrome; Aged; Biomarkers; Cause of Death; Diabetes Mellitus, Type 2; Female; Heart Failure; Humans; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Prospective Studies; Risk Assessment; Risk Factors; Stroke; Time Factors

Sodium glucose co-transporter 2 inhibitors may reduce cardiovascular and heart failure risk in patients with type 2 diabetes mellitus (T2DM).. The goal of this study was to examine the effects of canagliflozin on cardiovascular biomarkers in older patients with T2DM.. In 666 T2DM patients randomized to receive canagliflozin 100 or 300 mg or placebo, the study assessed the median percent change in serum N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity troponin I (hsTnI), soluble (s)ST2, and galectin-3 from baseline to 26, 52, and 104 weeks.. Both serum NT-proBNP and serum hsTnI levels increased in placebo recipients, but they remained largely unchanged in those randomized to canagliflozin. Hodges-Lehmann estimates of the difference in median percent change between pooled canagliflozin and placebo were -15.0%, -16.1%, and -26.8% for NT-proBNP, and -8.3%, -11.9%, and -10.0% for hsTnI at weeks 26, 52, and 104, respectively (all p < 0.05). Serum sST2 was unchanged with canagliflozin and placebo over 104 weeks. Serum galectin-3 modestly increased from baseline with canagliflozin versus placebo, with significant differences observed at 26 and 52 weeks but not at 104 weeks. These results remained unchanged when only patients with complete samples were assessed.. Compared with placebo, treatment with canagliflozin delayed the rise in serum NT-proBNP and hsTnI for over 2 years in older T2DM patients. These cardiac biomarker data provide support for the beneficial cardiovascular effect of sodium glucose co-transporter 2 inhibitors in T2DM. (A Safety and Efficacy Study of Canagliflozin in Older Patients [55 to 80 Years of Age] With Type 2 Diabetes Mellitus; NCT01106651).

Topics: Aged; Aged, 80 and over; Biomarkers; Blood Glucose; Canagliflozin; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Follow-Up Studies; Humans; Hypoglycemic Agents; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Time Factors; Troponin I

Subclinical myocardial injury, as measured by high-sensitivity cardiac troponin T (hsTnT), and myocardial stress, as measured by N-terminal pro-B-type natriuretic peptide (NT-proBNP), are related to glycemic control in patients with type 2 diabetes mellitus, and are strong predictors of adverse cardiovascular outcomes. We sought to determine whether antihyperglycemic therapy improves measures of myocardial injury and myocardial stress in patients with type 2 diabetes mellitus.. We randomized, in a 2×2 factorial fashion, 438 patients with type 2 diabetes mellitus to insulin glargine, metformin, the combination, or placebo and measured changes in NT-proBNP and hsTnT after 12 weeks of therapy. At baseline, the median (Q1-Q3) plasma concentration was 35.4 (15.7-86.3) ng/L for NT-proBNP and 6.7 (4.6-10.1) ng/L for hsTnT. The adjusted (95% confidence interval) change in NT-proBNP concentration was 20.7% (7.9-35.0) in the insulin arm compared with 0.13% (-10.8 to 12.5) in the no-insulin arm (. Insulin glargine was associated with a significant 20.7% increase in NT-proBNP, a marker of myocardial stress, after 12 weeks of therapy. No change in hsTnT, a marker of myocardial injury, was observed. The changes were independent of substantial improvements in glucose control.. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00366301.

Topics: Biomarkers; Blood Glucose; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin Glargine; Male; Metformin; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Risk Factors; Troponin T

To determine the effect of the glucagon-like peptide-1 analogue liraglutide on left ventricular function in chronic heart failure patients with and without type 2 diabetes.. LIVE was an investigator-initiated, randomised, double-blinded, placebo-controlled multicentre trial. Patients (n = 241) with reduced left ventricular ejection fraction (LVEF ≤45%) were recruited (February 2012 to August 2015). Patients were clinically stable and on optimal heart failure treatment. Intervention was liraglutide 1.8 mg once daily or matching placebo for 24 weeks. The LVEF was similar at baseline in the liraglutide and the placebo group (33.7 ± 7.6% vs. 35.4 ± 9.4%). Change in LVEF did not differ between the liraglutide and the placebo group; mean difference (95% confidence interval) was -0.8% (-2.1, 0.5; P = 0.24). Heart rate increased with liraglutide [mean difference: 7 b.p.m. (5, 9), P < 0.0001]. Serious cardiac events were seen in 12 (10%) patients treated with liraglutide compared with 3 (3%) patients in the placebo group (P = 0.04).. Liraglutide did not affect left ventricular systolic function compared with placebo in stable chronic heart failure patients with and without diabetes. Treatment with liraglutide was associated with an increase in heart rate and more serious cardiac adverse events, and this raises some concern with respect to the use of liraglutide in patients with chronic heart failure and reduced left ventricular function. More data on the safety of liraglutide in different subgroups of heart failure patients are needed.

Topics: Acute Coronary Syndrome; Aged; Atrial Fibrillation; Chronic Disease; Diabetes Mellitus, Type 2; Disease Progression; Double-Blind Method; Echocardiography; Female; Heart Failure; Heart Rate; Humans; Incretins; Liraglutide; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Stroke Volume; Tachycardia, Ventricular; Treatment Outcome; Ventricular Function, Left; Walk Test

Sodium glucose co-transporter 2 (SGLT2) inhibitors exhibit diuretic activity, which is a possible mechanism underlying the cardiovascular benefit of these inhibitors. However, the osmotic diuresis-induced increase in urine volume, and the risk of dehydration have been of concern with SGLT2 inhibitor treatment. This study aimed to investigate the mechanism underlying SGLT2 inhibitor canagliflozin-induced diuresis in Japanese type 2 diabetes mellitus (T2DM) patients.. Thirteen T2DM patients received a daily oral dose of 100 mg canagliflozin before breakfast for 6 days. Blood and urine samples were collected at predetermined time points. The primary endpoint was evaluation of correlations between changes from baseline in urine volume and factors that are known to affect urine volume and between actual urine volume and these factors.. Canagliflozin transiently increased urine volume and urinary sodium excretion on Day 1 with a return to baseline levels thereafter. Canagliflozin administration increased urinary glucose excretion, which was sustained during repeated-dose administration. Plasma atrial natriuretic peptide (ANP) and N-terminal pro-b-type natriuretic peptide (NT-proBNP) levels decreased, while plasma renin activity increased. On Day 1 of treatment, changes in sodium and potassium excretion were closely correlated with changes in urine output. A post hoc multiple regression analysis showed changes in sodium excretion and water intake as factors that affected urine volume change at Day 1. Furthermore, relative to that at baseline, canagliflozin decreased blood glucose throughout the day and increased plasma total GLP-1 after breakfast.. Canagliflozin induced transient sodium excretion and did not induce water intake at Day 1; hence, natriuresis rather than glucose-induced osmotic diuresis may be a major factor involved in the canagliflozin-induced transient increase in urine output. In addition, canagliflozin decreased plasma ANP and NT-proBNP levels and increased plasma renin activity, which may be a compensatory mechanism for sodium retention, leading to subsequent urine output recovery.. UMIN000019462.. Mitsubishi Tanabe Pharma Corporation.

Topics: Adult; Blood Glucose; Canagliflozin; Dehydration; Diabetes Mellitus, Type 2; Female; Glycosuria; Humans; Hypoglycemic Agents; Japan; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Sodium-Glucose Transporter 2; Sodium-Glucose Transporter 2 Inhibitors; Treatment Outcome

Use of dipeptidyl peptidase-4 inhibitors (DPP4-i) for the treatment of type 2 diabetes (T2D) has been associated with a possible increase in the risk for heart failure (HF). B-type natriuretic peptide (BNP), which is both a biomarker of HF and a hemodynamically active hormone, is a substrate of DPP-4. We herein tested the acute effects of the DPP-4i linagliptin on BNP and NT-proBNP in a cross-over placebo-controlled trial in patients with T2D with and without chronic kidney disease (CKD).. B-type natriuretic peptide and NT-proBNP were measured using commercially available clinical-grade immune-assays at baseline and at the end of a 4-day treatment with placebo and linagliptin. Changes from baseline during each treatment arm, as well as placebo-subtracted effects of linagliptin on BNP and NT-proBNP were calculated.. 46 patients completed the study, 18 of whom were affected by CKD. Baseline BNP and NT-proBNP levels increased with age, were elevated in CKD patients, and inversely correlated with estimated glomerular filtration rate. No significant change was detected in BNP and NT-proBNP levels after treatment with linagliptin or placebo in patients with or without CKD. Only in CKD patients the placebo-subtracted effect of linagliptin indicated a significant reduction in NT-proBNP levels, but this finding was not statistically robust.. Acute treatment with a DPP-4i exerts no clinically-meaningful effects on BNP and NT-proBNP. As routinely used immunoassays do not discriminate between intact/active and cleaved BNP, these data cannot rule out an effect of DPP-4i on HF pathophysiology. Trial registration NCT01617824.

Topics: Aged; Biomarkers; Cross-Over Studies; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Dipeptidyl Peptidase 4; Dipeptidyl-Peptidase IV Inhibitors; Female; Glomerular Filtration Rate; Humans; Immunoassay; Kidney; Linagliptin; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Renal Insufficiency, Chronic; Single-Blind Method; Time Factors; Treatment Outcome

To assess the effect of testosterone treatment on cardiac biomarkers in men with type 2 diabetes (T2D).. Randomized double-blind, parallel, placebo-controlled trial.. Men aged 35-70 years with T2D and a total testosterone level ≤12·0 nmol/l (346 ng/dl) at high risk of cardiovascular events, median 10-year United Kingdom Prospective Diabetes Study (UKPDS) coronary heart disease (CHD) risk 21% (IQR 16%, 27%). Eighty-eight participants were randomly assigned to 40 weeks of intramuscular testosterone undecanoate (n = 45) or matching placebo (n = 43).. N-terminal pro B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT).. Testosterone treatment reduced NT-proBNP (mean adjusted difference (MAD) in change over 40 weeks across the testosterone and placebo groups, -17·9 ng/l [95% CI -32·4, -3·5], P = 0·047), but did not change hs-cTnT (MAD, 0·41 ng/l (95% CI -0·56, 1·39), P = 0·62). Six men, three in each group experienced an adverse cardiac event, displaying already higher baseline NT-proBNP (P < 0·01) and hs-cTnT levels (P = 0·01). At baseline, 10-year UKPDS CHD risk was associated positively with NT-proBNP (τ = 0·21, P = 0·004) and hs-cTnT (τ = 0·23, P = 0·003) and inversely with testosterone (total testosterone τ = -0·18, P = 0·02, calculated free testosterone τ = -0·19, P = 0·01), but there was no significant association between testosterone and cardiac biomarkers (P > 0·05).. In this trial of men with T2D and high cardiovascular risk, testosterone treatment reduced NT-proBNP and did not change hs-cTnT. Further studies should determine whether men with increased cardiac biomarkers prior to testosterone therapy are at higher risk of testosterone treatment-associated adverse cardiac events.

Topics: Adult; Aged; Biomarkers; Coronary Disease; Diabetes Mellitus, Type 2; Double-Blind Method; Humans; Male; Middle Aged; Myocardium; Natriuretic Peptide, Brain; Outcome Assessment, Health Care; Peptide Fragments; Prospective Studies; Risk Factors; Testosterone; Time Factors; Troponin T; United Kingdom

GLP-1 receptor (GLP-1R) agonists induce natriuresis and reduce blood pressure (BP) through incompletely understood mechanisms. We examined the effects of acute and 21-day administration of liraglutide on plasma atrial natriuretic peptide (ANP), urinary sodium excretion, office and 24-h BP, and heart rate (HR).. Liraglutide or placebo was administered for 3 weeks to hypertensive subjects with type 2 diabetes in a double-blinded, randomized, placebo-controlled crossover clinical trial in the ambulatory setting. End points included within-subject change from baseline in plasma ANP, Nt-proBNP, office BP, and HR at baseline and over 4 h following a single dose of liraglutide (0.6 mg) and after 21 days of liraglutide (titrated to 1.8 mg) versus placebo administration. Simultaneous 24-h ambulatory BP and HR monitoring and 24-h urine collections were measured at baseline and following 21 days of treatment.. Plasma ANP levels did not change significantly after acute (+16.72 pg/mL, P = 0.24, 95% CI [-12.1, +45.5] at 2 h) or chronic (-17.42 pg/mL, 95% CI [-36.0, +1.21] at 2 h) liraglutide administration. Liraglutide significantly increased 24-h and nighttime urinary sodium excretion; however, 24-h systolic BP was not significantly different. Small but significant increases in 24-h and nighttime diastolic BP and HR were observed with liraglutide. Body weight, HbA1c, and cholesterol were lower, and office-measured HR was transiently increased (for up to 4 h) with liraglutide administration.. Sustained liraglutide administration for 3 weeks increases urinary sodium excretion independent of changes in ANP or BP in overweight and obese hypertensive patients with type 2 diabetes.

Topics: Adult; Aged; Atrial Natriuretic Factor; Blood Pressure; Body Weight; Cross-Over Studies; Diabetes Mellitus, Type 2; Double-Blind Method; Endpoint Determination; Female; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Heart Rate; Humans; Hypertension; Liraglutide; Male; Middle Aged; Natriuresis; Natriuretic Peptide, Brain; Obesity; Peptide Fragments; Receptors, Glucagon; Sodium

Serum carbamylated albumin (C-Alb) levels are associated with excess mortality in patients with diabetic end-stage renal disease. To gain insight into the pathophysiology of carbamylation, we determined associations between C-Alb and causes of death in patients on chronic hemodialysis. The Die Deutsche Diabetes Dialyse Studie (4D study) was a randomized controlled trial testing the effects of atorvastatin on survival in diabetic patients on dialysis during a median follow-up of 4 years. We stratified 1161 patients by C-Alb to see whether differences in carbamylation altered the effects of atorvastatin on survival. Baseline C-Alb significantly correlated with serum cardiac stress markers troponin T and N-terminal pro-B-type-natriuretic peptide and was associated with a history of heart failure and arrhythmia. C-Alb was strongly associated with 1-year adjusted risk of cardiovascular mortality, sudden cardiac death, and the 4-year risk of death from congestive heart failure (hazard ratios of 3.06, 3.78, and 4.64, respectively) but not with myocardial infarction or stroke. Patients with low C-Alb, treated with atorvastatin, experienced a significant improvement in their 4-year survival (hazard ratio 0.692). High C-Alb levels are associated with ongoing cardiac damage, risk of congestive heart failure, and sudden cardiac death. Thus, carbamylation and uremic cardiomyopathy are associated in patients with diabetes mellitus and kidney disease. In addition, statins were specifically beneficial to hemodialysis patients with low C-Alb.

Topics: Aged; Atorvastatin; Atrial Fibrillation; Cause of Death; Cholesterol; Comorbidity; Death, Sudden, Cardiac; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Female; Heart Failure; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertension; Kidney Failure, Chronic; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Renal Dialysis; Risk Factors; Serum Albumin; Survival Rate; Troponin T; Uremia

To investigate the safety and potential efficacy of the novel non-steroidal mineralocorticoid receptor antagonist finerenone in patients with worsening chronic heart failure and reduced left ventricular ejection fraction (HFrEF) and at high risk of hyperkalaemia and worsening renal dysfunction.. The MinerAlocorticoid Receptor antagonist Tolerability Study-Heart Failure (ARTS-HF; NCT01807221) is a multicentre, randomized, double-blind, active-comparator-controlled, six-parallel-group, phase 2b dose-finding study. In total, 1060 patients with HFrEF and concomitant type 2 diabetes mellitus and/or chronic kidney disease (CKD) will be randomized within 7 days of emergency presentation to hospital for worsening chronic HF to receive finerenone (one of five doses in the range 2.5-20.0 mg once daily) or eplerenone (25 mg every second day to 50 mg once daily for 90 days). The primary objective is to investigate the safety and potential efficacy (measured as the percentage of individuals with a decrease in plasma N-terminal pro-B-type natriuretic peptide [NT-proBNP] of more than 30% relative to baseline at day 90 ± 2) of different oral doses of finerenone compared with eplerenone. Other objectives are to assess the effects of finerenone on a composite clinical endpoint (death from any cause, cardiovascular hospitalizations, or emergency presentations for worsening chronic HF), and on changes in health-related quality of life from baseline.. ARTS-HF is the first phase 2b clinical trial to investigate the effects of finerenone on plasma NT-proBNP in a high-risk population of patients who have worsening chronic HF with type 2 diabetes mellitus and/or CKD presenting at the emergency department.

Topics: Comorbidity; Diabetes Mellitus, Type 2; Double-Blind Method; Eplerenone; Heart Failure; Humans; Mineralocorticoid Receptor Antagonists; Naphthyridines; Natriuretic Agents; Natriuretic Peptide, Brain; Peptide Fragments; Renal Insufficiency, Chronic; Spironolactone

The EXAMINE trial showed non-inferiority of the DPP-4 inhibitor alogliptin to placebo on major adverse cardiac event (MACE) rates in patients with type 2 diabetes and recent acute coronary syndromes. Concerns about excessive rates of in-hospital heart failure in another DPP-4 inhibitor trial have been reported. We therefore assessed hospital admission for heart failure in the EXAMINE trial.. Patients with type 2 diabetes and an acute coronary syndrome event in the previous 15-90 days were randomly assigned alogliptin or placebo plus standard treatment for diabetes and cardiovascular disease prevention. The prespecified exploratory extended MACE endpoint was all-cause mortality, non-fatal myocardial infarction, non-fatal stroke, urgent revascularisation due to unstable angina, and hospital admission for heart failure. The post-hoc analyses were of cardiovascular death and hospital admission for heart failure, assessed by history of heart failure and brain natriuretic peptide (BNP) concentration at baseline. We also assessed changes in N-terminal pro-BNP (NT-pro-BNP) from baseline to 6 months. This study is registered with ClinicalTrials.gov, number NCT00968708.. 5380 patients were assigned to alogliptin (n=2701) or placebo (n=2679) and followed up for a median of 533 days (IQR 280-751). The exploratory extended MACE endpoint was seen in 433 (16·0%) patients assigned to alogliptin and in 441 (16·5%) assigned to placebo (hazard ratio [HR] 0·98, 95% CI 0·86-1·12). Hospital admission for heart failure was the first event in 85 (3·1%) patients taking alogliptin compared with 79 (2·9%) taking placebo (HR 1·07, 95% CI 0·79-1·46). Alogliptin had no effect on composite events of cardiovascular death and hospital admission for heart failure in the post hoc analysis (HR 1·00, 95% CI 0·82-1·21) and results did not differ by baseline BNP concentration. NT-pro-BNP concentrations decreased significantly and similarly in the two groups.. In patients with type 2 diabetes and recent acute coronary syndromes, alogliptin did not increase the risk of heart failure outcomes.. Takeda Development Center Americas.

Topics: Acute Coronary Syndrome; Aged; Angina, Unstable; Diabetes Mellitus, Type 2; Diabetic Cardiomyopathies; Double-Blind Method; Female; Heart Failure; Hospitalization; Humans; Hypoglycemic Agents; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Peptide Fragments; Piperidines; Risk Factors; Stroke; Uracil

Topics: Adamantane; Aged; Diabetes Mellitus, Type 2; Echocardiography, Doppler; Electrocardiography; Female; Follow-Up Studies; Glomerular Filtration Rate; Glycated Hemoglobin; Heart Function Tests; Humans; Incretins; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Nitriles; Pyrrolidines; Reference Values; Risk Assessment; Stroke Volume; Treatment Outcome; Vildagliptin

It remains uncertain whether diabetes itself causes specific echocardiographic features of myocardial morphology and function in the absence of hypertension or ischemic heart disease. The purpose of the present study was to determine the characteristics of pure diabetic cardiomyopathy-related echocardiographic morphology and function using layer-by-layer evaluation with myocardial strain echocardiography.. We enrolled 104 patients with poorly controlled type 2 diabetes mellitus (mean HbA1c level, 10%) with (n=74) or without (n=40) hypertension and 24 age- and sex-matched healthy volunteers. Patients with coronary artery stenosis or structural heart disease were excluded. Myocardial layer-specific strain was analyzed by speckle tracking echocardiography. Compared with the healthy control group, the normotensive diabetes group showed no significant difference in ejection fraction, left ventricular mass index, diastolic properties, left atrial volume index, or B-type natriuretic protein (BNP) level, but global longitudinal strain and subendocardial radial strain were significantly deteriorated. The deterioration of longitudinal strain correlated with body mass index (R=0.49, P<0.01) and blood pressure (R=0.36, P<0.01) in the normotensive diabetes group.. Deterioration of left ventricular longitudinal shortening accompanied by decreased subendocardial wall thickening are the characteristic functional abnormalities of diabetic cardiomyopathy in patients without hypertrophy, diastolic dysfunction, or elevated BNP. Obesity and blood pressure may also play important roles in this strain abnormality in asymptomatic patients with type 2 diabetes.

Topics: Adult; Aged; Blood Pressure; Diabetes Mellitus, Type 2; Diabetic Cardiomyopathies; Female; Humans; Hypertension; Male; Middle Aged; Myocardium; Natriuretic Peptide, Brain; Obesity

Endothelin A receptor antagonists (ERAs) decrease residual albuminuria in patients with diabetic kidney disease; however, their clinical utility may be limited by fluid retention. Consequently, the primary objective of this study was to identify predictors for ERA-induced fluid retention among patients with type 2 diabetes and CKD. A secondary objective was to determine if the degree of fluid retention necessarily correlated with the magnitude of albuminuria reduction in those patients receiving ERAs.. A post hoc analysis was conducted of the phase IIb atrasentan trials assessing albuminuria reduction in 211 patients with type 2 diabetes, urine albumin/creatinine ratios of 300-3500 mg/g, and eGFRs of 30-75 ml/min per 1.73 m(2) who were randomly assigned to receive placebo (n=50) or atrasentan 0.75 mg/d (n=78) or 1.25 mg/d (n=83) for 12 weeks. Changes in body weight and hemoglobin (Hb) after 2 weeks of treatment were used as surrogate markers of fluid retention.. Baseline predictors of weight gain after 2 weeks of atrasentan treatment were higher atrasentan dose, lower eGFR, higher glycated hemoglobin, higher systolic BP, and lower homeostatic metabolic assessment product. Higher atrasentan dose and lower eGFR also predicted decreases in Hb. There were no changes in B-type natriuretic peptide. There was no correlation between reduction in albuminuria after 2 weeks of atrasentan treatment and changes in body weight or Hb.. In the Reducing Residual Albuminuria in Subjects With Diabetes and Nephropathy With Atrasentan/JAPAN trials, atrasentan-associated fluid retention was more likely in patients with diabetes and nephropathy who had lower eGFR or received a higher dose of atrasentan. Finding that albuminuria reduction was not associated with changes in body weight and Hb suggests that the albuminuria-reducing efficacy of atrasentan is not impaired by fluid retention.

Topics: Aged; Albuminuria; Atrasentan; Body Fluids; Creatinine; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Double-Blind Method; Endothelin Receptor Antagonists; Female; Glomerular Filtration Rate; Glycated Hemoglobin; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Pyrrolidines; Weight Gain

Statins have beneficial effects on cardiovascular morbidity and mortality independently of reduction of plasma cholesterol.. In patients with type 2 diabetes and nephropathy, chronic kidney disease stage II-III, we tested the hypothesis that atorvastatin increased systemic and renal nitric oxide (NO) availability using L-NMMA as an inhibitor of NO production. We performed a randomized, placebo-controlled, crossover study, using atorvastatin/placebo treatment for five days with a standardized diet and fluid intake. We measured brachial BP (bBP), central BP (cBP), GFR, urinary output (OU), free water clearance (CH2O), fractional excretion of sodium (FENa), urinary excretion of albumin (UAER and UACR), AQP2 (u-AQP2) and ENaC (u-ENaCγ) and plasma concentrations of vasoactive hormones: renin, angiotensin II, aldosterone, arginine vasopressin, endothelin-1 and brain natriuretic peptide.. During atorvastatin and placebo treatment, L-NMMA infusion, changed the effect variables significantly, but to the same extent, i.e. an increase in bBP and cBP, and a decrease in GFR, OU, CH2O, FENa, u-AQP2 and u-ENaCγ. In addition, renin and angiotensin II was reduced, aldosterone increased, and vasopressin, endothelin-1 and brain natriuretic hormone unchanged.. During, atorvastatin and placebo treatment, inhibition of nitric oxide synthesis induced the same response in brachial and central blood pressure, GFR, renal tubular function and vasoactive hormones. Thus, atorvastatin did not change nitric oxide availability in type 2 diabetics with nephropathy.

Topics: Aged; Arginine Vasopressin; Atorvastatin; Atrial Natriuretic Factor; Blood Pressure; Cross-Over Studies; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Glomerular Filtration Rate; Heart Rate; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Kidney Tubules; Male; Middle Aged; Natriuretic Peptide, Brain; Nitric Oxide; omega-N-Methylarginine; Pulse Wave Analysis; Pyrroles; Renal Insufficiency, Chronic; Treatment Outcome; Vascular Stiffness; Vasopressins

We aimed to study the relationship between measures of adiposity, insulin sensitivity and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in the Diabetes Prevention Program (DPP).. The DPP is a completed clinical trial. Using stored samples from this resource, we measured BMI, waist circumference (WC), an insulin sensitivity index (ISI; [1/HOMA-IR]) and NT-proBNP at baseline and at 2 years of follow-up in participants randomised to placebo (n = 692), intensive lifestyle intervention (n = 832) or metformin (n = 887).. At baseline, log NT-proBNP did not differ between treatment arms and was correlated with baseline log ISI (p < 0.0001) and WC (p = 0.0003) but not with BMI (p = 0.39). After 2 years of treatment, BMI decreased in the lifestyle and metformin groups (both p < 0.0001); WC decreased in all three groups (p < 0.05 for all); and log ISI increased in the lifestyle and metformin groups (both p < 0.001). The change in log NT-proBNP did not differ in the lifestyle or metformin group vs the placebo group (p > 0.05 for both). In regression models, the change in log NT-proBNP was positively associated with the change in log ISI (p < 0.005) in all three study groups after adjusting for changes in BMI and WC, but was not associated with the change in BMI or WC after adjusting for changes in log ISI.. Circulating NT-proBNP was associated with a measure of insulin sensitivity before and during preventive interventions for type 2 diabetes in the DPP. This relationship persisted after adjustment for measures of adiposity and was consistent regardless of whether a participant was treated with placebo, intensive lifestyle intervention or metformin.

Topics: Adipose Tissue; Adiposity; Adult; Blood Glucose; Body Mass Index; Diabetes Mellitus; Diabetes Mellitus, Type 2; Female; Humans; Insulin; Insulin Resistance; Life Style; Male; Metformin; Middle Aged; Natriuretic Peptide, Brain; Obesity; Peptide Fragments; Regression Analysis

Diabetes mellitus and heart failure frequently coexist. However, few diabetes mellitus trials have prospectively evaluated and adjudicated heart failure as an end point.. A total of 16 492 patients with type 2 diabetes mellitus and a history of, or at risk of, cardiovascular events were randomized to saxagliptin or placebo (mean follow-up, 2.1 years). The primary end point was the composite of cardiovascular death, myocardial infarction, or ischemic stroke. Hospitalization for heart failure was a predefined component of the secondary end point. Baseline N-terminal pro B-type natriuretic peptide was measured in 12 301 patients. More patients treated with saxagliptin (289, 3.5%) were hospitalized for heart failure compared with placebo (228, 2.8%; hazard ratio, 1.27; 95% confidence intercal, 1.07-1.51; P=0.007). Corresponding rates at 12 months were 1.9% versus 1.3% (hazard ratio, 1.46; 95% confidence interval, 1.15-1.88; P=0.002), with no significant difference thereafter (time-varying interaction, P=0.017). Subjects at greatest risk of hospitalization for heart failure had previous heart failure, an estimated glomerular filtration rate ≤60 mL/min, or elevated baseline levels of N-terminal pro B-type natriuretic peptide. There was no evidence of heterogeneity between N-terminal pro B-type natriuretic peptide and saxagliptin (P for interaction=0.46), although the absolute risk excess for heart failure with saxagliptin was greatest in the highest N-terminal pro B-type natriuretic peptide quartile (2.1%). Even in patients at high risk of hospitalization for heart failure, the risk of the primary and secondary end points were similar between treatment groups.. In the context of balanced primary and secondary end points, saxagliptin treatment was associated with an increased risk or hospitalization for heart failure. This increase in risk was highest among patients with elevated levels of natriuretic peptides, previous heart failure, or chronic kidney disease.. http://www.clinicaltrials.gov. Unique identifier: NCT01107886.

Topics: Adamantane; Aged; C-Reactive Protein; Diabetes Mellitus, Type 2; Dipeptides; Dipeptidyl-Peptidase IV Inhibitors; Female; Follow-Up Studies; Heart Failure; Hospitalization; Humans; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Peptide Fragments; Risk Assessment; Troponin T

A phase 3 randomized clinical trial was designed to test whether bardoxolone methyl, a nuclear factor erythroid-2-related factor 2 (Nrf2) activator, slows progression to end-stage renal disease in patients with stage 4 chronic kidney disease and type 2 diabetes mellitus. The trial was terminated because of an increase in heart failure in the bardoxolone methyl group; many of the events were clinically associated with fluid retention.. We randomized 2,185 patients with type 2 diabetes mellitus (T2DM) and stage 4 chronic kidney disease (CKD) (estimated glomerular filtration rate 15 to <30 mL min(-1) 1.73 m(-2)) to once-daily bardoxolone methyl (20 mg) or placebo. We used classification and regression tree analysis to identify baseline factors predictive of heart failure or fluid overload events. Elevated baseline B-type natriuretic peptide and previous hospitalization for heart failure were identified as predictors of heart failure events; bardoxolone methyl increased the risk of heart failure by 60% in patients with these risk factors. For patients without these baseline characteristics, the risk for heart failure events among bardoxolone methyl- and placebo-treated patients was similar (2%). The same risk factors were also identified as predictors of fluid overload and appeared to be related to other serious adverse events.. Bardoxolone methyl contributed to events related to heart failure and/or fluid overload in a subpopulation of susceptible patients with an increased risk for heart failure at baseline. Careful selection of participants and vigilant monitoring of the study drug will be required in any future trials of bardoxolone methyl to mitigate the risk of heart failure and other serious adverse events.

Topics: Aged; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Administration Schedule; Early Termination of Clinical Trials; Female; Follow-Up Studies; Glomerular Filtration Rate; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Oleanolic Acid; Patient Safety; Predictive Value of Tests; Reference Values; Renal Insufficiency, Chronic; Risk Factors; Severity of Illness Index; Survival Rate; Treatment Outcome

The study sought to assess the primary preventive effect of neurohumoral therapy in high-risk diabetic patients selected by N-terminal pro-B-type natriuretic peptide (NT-proBNP).. Few clinical trials have successfully demonstrated the prevention of cardiac events in patients with diabetes. One reason for this might be an inaccurate selection of patients. NT-proBNP has not been assessed in this context.. A total of 300 patients with type 2 diabetes, elevated NT-proBNP (>125 pg/ml) but free of cardiac disease were randomized. The "control" group was cared for at 4 diabetes care units; the "intensified" group was additionally treated at a cardiac outpatient clinic for the up-titration of renin-angiotensin system (RAS) antagonists and beta-blockers. The primary endpoint was hospitalization/death due to cardiac disease after 2 years.. At baseline, the mean age of the patients was 67.5 ± 9 years, duration of diabetes was 15 ± 12 years, 37% were male, HbA1c was 7 ± 1.1%, blood pressure was 151 ± 22 mm Hg, heart rate was 72 ± 11 beats/min, median NT-proBNP was 265.5 pg/ml (interquartile range: 180.8 to 401.8 pg/ml). After 12 months there was a significant difference between the number of patients treated with a RAS antagonist/beta-blocker and the dosage reached between groups (p < 0.0001). Blood pressure was significantly reduced in both (p < 0.05); heart rate was only reduced in the intensified group (p = 0.004). A significant reduction of the primary endpoint (hazard ratio: 0.351; 95% confidence interval: 0.127 to 0.975, p = 0.044) was visible in the intensified group. The same was true for other endpoints: all-cause hospitalization, unplanned cardiovascular hospitalizations/death (p < 0.05 for all).. Accelerated up-titration of RAS antagonists and beta-blockers to maximum tolerated dosages is an effective and safe intervention for the primary prevention of cardiac events for diabetic patients pre-selected using NT-proBNP. (Nt-proBNP Guided Primary Prevention of CV Events in Diabetic Patients [PONTIAC]; NCT00562952).

Topics: Aged; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Biomarkers; Blood Pressure; Diabetes Mellitus, Type 2; Female; Heart Diseases; Heart Rate; Hospitalization; Humans; Kaplan-Meier Estimate; Male; Natriuretic Peptide, Brain; Peptide Fragments; Primary Prevention; Prospective Studies

Aim of this study was to compare the antiproteinuric effect of imidapril (I) and ramipril (R) in diabetic hypertensive patients with microalbuminuria.. One hundred and seventy-six patients were randomised to I 10 - 20 mg once daily (od) (n = 88) or R 5 - 10 mg od (n = 88) for 24 weeks. Clinic, ambulatory, central blood pressure (BP), urinary albumin excretion (UAE), plasma Angiotensin II (Ang II), bradykinin and brain natriuretic peptide (BNP) were assessed at baseline and after 6, 12 and 24 weeks.. Both I and R produced a similar decrease in clinic, ambulatory and central BP (p < 0.001 vs baseline). Both treatments significantly reduced UAE throughout the study, but the decrease in UAE associated with I was more pronounced, being evident at week 6 (p = 0.05) and maximal at week 24 end-point (-42 vs -29%, p < 0.01). BNP and Ang II levels were similarly reduced by I and R, while bradykinin increased more with R (+132 vs +86%, p < 0.05).. These findings showed that in diabetic hypertensive patients with microalbuminuria, despite equivalent BP-lowering effect, I produced a greater antiproteinuric effect than R, which might be due to different intrinsic molecular properties of the two drugs.

Topics: Adult; Aged; Albumins; Albuminuria; Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Bradykinin; Diabetes Mellitus, Type 2; Female; Humans; Hypertension; Imidazolidines; Male; Middle Aged; Natriuretic Peptide, Brain; Prospective Studies; Ramipril; Treatment Outcome

Look AHEAD (Action for Health in Diabetes) is a randomized trial determining whether intensive lifestyle intervention (ILI) aimed at long-term weight loss and increased physical fitness reduces cardiovascular morbidity and mortality in overweight and obese individuals with type 2 diabetes compared to control (diabetes support and education, DSE). We investigated the correlates of N-terminal pro-brain natriuretic peptide (NT-proBNP), a biomarker associated with heart failure (HF) risk, in a subsample from 15 of 16 participating centers and tested the hypothesis that ILI decreased NT-proBNP levels. Baseline and 1-year blood samples were assayed for NT-proBNP in a random sample of 1,500 without, and all 628 with, self-reported baseline CVD (cardiovascular disease) (N = 2,128). Linear models were used to assess relationships that log-transformed NT-proBNP had with CVD risk factors at baseline and that 1-year changes in NT-proBNP had with intervention assignment. At baseline, the mean (s.d.) age, BMI, and hemoglobin A(1c) (HbA(1c)) were 59.6 (6.8) years, 36.0 kg/m(2) (5.8), and 7.2% (1.1), respectively. Baseline geometric mean NT-proBNP was not different by condition (ILI 53.3 vs. DSE 51.5, P = 0.45), was not associated with BMI, and was inversely associated with HbA(1c). At 1 year, ILI participants achieved an average weight loss of 8.3% compared to 0.7% in DSE. At 1 year, NT-proBNP levels increased to a greater extent in the intervention arm (ILI +21.3% vs. DSE +14.2%, P = 0.046). The increased NT-proBNP associated with ILI was correlated with changes in HbA(1c), BMI, and body composition. In conclusion, among overweight and obese persons with diabetes, an ILI that reduced weight was associated with an increased NT-proBNP.

Topics: Biomarkers; Body Mass Index; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Glycated Hemoglobin; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Obesity; Overweight; Peptide Fragments; Predictive Value of Tests; Risk Reduction Behavior; Time Factors; Weight Loss

No previous studies have compared the DPP-4 inhibitors vildagliptin and sitagliptin in terms of blood glucose levels using continuous glucose monitoring (CGM) and cardiovascular parameters.. Twenty patients with type 2 diabetes mellitus were randomly allocated to groups who received vildagliptin then sitagliptin, or vice versa. Patients were hospitalized at 1 month after starting each drug, and CGM was used to determine: 1) mean (± standard deviation) 24-hour blood glucose level, 2) mean amplitude of glycemic excursions (MAGE), 3) fasting blood glucose level, 4) highest postprandial blood glucose level and time, 5) increase in blood glucose level after each meal, 6) area under the curve (AUC) for blood glucose level ≥180 mg/dL within 3 hours after each meal, and 7) area over the curve (AOC) for daily blood glucose level <70 mg/dL. Plasma glycosylated hemoglobin (HbA1c), glycoalbumin (GA), 1,5-anhydroglucitol (1,5AG), immunoreactive insulin (IRI), C-peptide immunoreactivity (CPR), brain natriuretic peptide (BNP), and plasminogen activator inhibitor-1 (PAI-1) levels, and urinary CPR levels, were measured.. The mean 24-hour blood glucose level was significantly lower in patients taking vildagliptin than sitagliptin (142.1 ± 35.5 vs. 153.2 ± 37.0 mg/dL; p = 0.012). In patients taking vildagliptin, MAGE was significantly lower (110.5 ± 33.5 vs. 129.4 ± 45.1 mg/dL; p = 0.040), the highest blood glucose level after supper was significantly lower (206.1 ± 40.2 vs. 223.2 ± 43.5 mg/dL; p = 0.015), the AUC (≥180 mg/dL) within 3 h was significantly lower after breakfast (484.3 vs. 897.9 mg/min/dL; p = 0.025), and urinary CPR level was significantly higher (97.0 ± 41.6 vs. 85.2 ± 39.9 μg/day; p = 0.008) than in patients taking sitagliptin. There were no significant differences in plasma HbA1c, GA, 1,5AG, IRI, CPR, BNP, or PAI-1 levels between patients taking vildagliptin and sitagliptin.. CGM showed that mean 24-h blood glucose, MAGE, highest blood glucose level after supper, and hyperglycemia after breakfast were significantly lower in patients with type 2 diabetes mellitus taking vildagliptin than those taking sitagliptin. There were no significant differences in BNP and PAI-1 levels between patients taking vildagliptin and sitagliptin.. UMIN000007687.

Topics: Adamantane; Adult; Aged; Biomarkers; Blood Glucose; C-Peptide; Cross-Over Studies; Deoxyglucose; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Drug Administration Schedule; Female; Glycated Hemoglobin; Glycated Serum Albumin; Glycation End Products, Advanced; Humans; Japan; Male; Middle Aged; Monitoring, Ambulatory; Natriuretic Peptide, Brain; Nitriles; Pilot Projects; Plasminogen Activator Inhibitor 1; Postprandial Period; Predictive Value of Tests; Pyrazines; Pyrrolidines; Serum Albumin; Sitagliptin Phosphate; Time Factors; Treatment Outcome; Triazoles; Vildagliptin

According to previous studies endogenous ouabain (EO) closely correlates with high blood pressure, congestive heart failure and kidney disease in humans. Our aims were to analyse associations between plasma, urinary EO level and various markers of cardiovascular damage in treated hypertensive patients. Forty-one adult patients with hypertension and/or diabetes mellitus (DM) and/or chronic kidney disease (CKD) were studied. We assessed plasma and urinary EO, pro-brain natriuretic peptide and catecholamines, profile of ambulatory blood pressure monitor and cardiovascular status by echocardiography and echo-tracking. The highest level of plasma EO (19.7±9.5 pmol l⁻¹) was measured in hypertensive patients with DM and CKD. The nighttime mean arterial blood pressure independently correlated with the level of plasma EO (P=0.004), while independent predictor of the β-stiffness of carotid artery was the urinary EO (P=0.011). Elevated level of EO was associated with nighttime blood pressure and subclinical organ damage in treated hypertensive patients, suggesting possible role of EO in the pathogenesis of impaired diurnal blood pressure rhythm and arterial stiffness.

Topics: Aged; Antihypertensive Agents; Biomarkers; Blood Pressure Monitoring, Ambulatory; Carotid Artery, Common; Catecholamines; Chronic Disease; Circadian Rhythm; Diabetes Mellitus, Type 2; Echocardiography; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Kidney Diseases; Male; Middle Aged; Natriuretic Peptide, Brain; Ouabain; Peptide Fragments; Risk Factors

Angiotensin II type 1 (AT1) receptor antagonists (angiotensin receptor blockers [ARBs]) are widely used for the treatment of not only hypertension but also cardiac dysfunction. B-type natriuretic peptide (BNP) is secreted mainly by the cardiac ventricle and plays an important role in the regulation of blood pressure (BP) and body fluid. It has been established that the plasma level of BNP is increased in patients with chronic heart failure in proportion to the severity of cardiac dysfunction. Because cardiac dysfunction is closely associated with a high risk of mortality in patients with diabetes mellitus, early identification and prevention of cardiac dysfunction are important. The objective of this study was to determine the effects of olmesartan medoxomil, a novel ARB, on the plasma level of BNP in hypertensive patients with type 2 diabetes.. This was a preliminary, prospective, observational, open-label study. Sixty-eight type 2 diabetic patients with hypertension (systolic BP [SBP]≥140 mmHg or diastolic BP [DBP]≥90 mmHg) received olmesartan medoxomil 10–20 mg/day for 24 weeks. Plasma levels of BNP, as well as several clinical parameters of glycaemic control and lipid metabolism, were compared before and after 24 weeks of treatment. Another group consisting of 22 age- and body mass index-matched subjects not treated with olmesartan medoxomil was observed for reference purposes.. In the olmesartan medoxomil group, mean±SD SBP decreased from 152.8±16.4 at baseline to 146.8±14.4 mmHg after 24 weeks' treatment (p<0.05); similarly, mean±SD DBP decreased from 85.6±10.5 to 81.3±11.6 mmHg (p<0.05). In 53 subjects in whom plasma levels of BNP could be measured both before and after treatment, mean±SD BNP decreased from 41.3±49.9 to 32.5±36.3 pg/mL (p<0.05). Change in plasma BNP level over the 24-week treatment period in the olmesartan medoxomil group was not correlated with change in SBP or DBP. Multiple regression analysis revealed that change in plasma BNP level was not correlated with baseline value of or change in any other parameters. No other parameters in the olmesartan medoxomil group, and no parameters in the non-olmesartan medoxomil reference group, showed significant changes.. The current preliminary study showed that olmesartan medoxomil treatment might decrease plasma BNP levels, independent of its BP-lowering effect, in hypertensive patients with type 2 diabetes.

Topics: Aged; Angiotensin II Type 1 Receptor Blockers; Blood Pressure; Diabetes Mellitus, Type 2; Female; Humans; Hypertension; Imidazoles; Male; Middle Aged; Natriuretic Peptide, Brain; Olmesartan Medoxomil; Prospective Studies; Tetrazoles

Thiazolidinediones cause peripheral oedema, the aetiology of which remains poorly understood.. In a sub-study of a 6-month trial comparing rosiglitazone (Rsg) versus placebo, we compared those with versus without oedema among the 74 subjects treated with Rsg with respect to peak oxygen consumption indexed to fat-free mass (VO(2peak-FFM) ), cardiac MRI and markers of plasma volume expansion.. Almost half (49%) of the Rsg-treated patients developed oedema. Baseline VO(2peak-FFM) was not different between those with versus without oedema (25.8 versus 28.2 ml/kg/min; p = 0.22) and declined 5% in the oedema group (Δ -1.3 ml/min/kg; p = 0.005) with no change in those without oedema. Stroke volume increased in both groups (Δ 8.7 and 8.8 ml; p < 0.001 for each); end-diastolic volume increased only in those with oedema (+13.1 ml; p = 0.001). No other cardiac function changes were observed. In both groups, weight increased (3.6 and 2.2 kg) and haematocrit decreased (-3.2% and -2.1%; p < 0.001 for each). In those with oedema, albumin decreased (-0.2 g/dl) and brain natriuretic peptide increased (11.9 pg/ml; p < 0.03 for each).. Oedema was associated with a small decline in VO(2peak FFM), no adverse effects on cardiac function, and changes in selected measures suggesting that volume expansion underpins Rsg oedema.

Topics: Aged; Biomarkers; Chi-Square Distribution; Diabetes Mellitus, Type 2; Edema; Exercise Test; Female; Heart Failure; Hematocrit; Humans; Hypoglycemic Agents; Magnetic Resonance Imaging; Male; Middle Aged; Myocardium; Natriuretic Peptide, Brain; Oxygen Consumption; Plasma Volume; Prospective Studies; Rosiglitazone; Serum Albumin; Single-Blind Method; Stroke Volume; Texas; Thiazolidinediones; Time Factors; Ventricular Function; Weight Gain

Patients with type 2 diabetes (T2DM) have a high restenosis rate after percutaneous coronary intervention (PCI). This study investigated whether markers of inflammation and the adipo-insular axis associated with T2DM and poor metabolic control were able to predict restenosis after PCI in T2DM patients.. The predictive value of traditional and non-traditional risk markers, including IL-1β, IL-6, TNF-α, hsCRP, interferon gamma, leptin, IGF-I, insulin, proinsulin and NT-proBNP, was investigated in 82 patients with T2DM. A re-angiography 6 months after the index percutaneous coronary intervention (PCI) revealed that 43% of the patients had a restenosis. In a multiple regression analysis, the only independent predictors of restenosis were fasting glucose before the PCI and previous myocardial infarction (odds ratio [OR] 1.44, 95% confidence interval [CI] 1.07-1.92; p = 0.015 and OR 8.00, 95% CI 2.49-25.67; p ≤ 0.001, respectively). None of the other markers remained as significant predictors.. Fasting glucose prior to the PCI was an independent predictor of restenosis in patients with T2DM while analyses of a variety of markers related to inflammation and the adipo-insular axis did not add any further information.

Topics: Aged; Angioplasty, Balloon, Coronary; Biomarkers; Blood Glucose; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Cytokines; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Inflammation Mediators; Insulin; Insulin-Like Growth Factor I; Leptin; Logistic Models; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Odds Ratio; Peptide Fragments; Proinsulin; Prospective Studies; Risk Assessment; Risk Factors; Sweden; Time Factors; Treatment Outcome

Adipocyte fatty acid-binding protein (A-FABP) has been shown to play important roles in the development of metabolic syndrome, diabetes, and cardiovascular diseases. In this study we investigated the possible role of A-FABP in the development of cardiac dysfunction related to rosiglitazone treatment.. A total of 84 patients with newly diagnosed type 2 diabetes were treated with rosiglitazone for 48 weeks. Circulating A-FABP and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels were determined at baseline and repeated at 24 and 48 weeks. After the 48-week rosiglitazone treatment period, serum levels of both A-FABP and NT-proBNP increased progressively and significantly (P<0.01). Serum levels of A-FABP were demonstrated to be positively correlated with gender and waist circumference both at baseline and the end of the study, and with age, body mass index (BMI), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and NT-proBNP at 48 weeks (all P<0.05). In addition, changes in A-FABP were significantly and positively correlated with changes in NT-proBNP (r = 0.239, P = 0.039). Furthermore, multiple stepwise regression analysis showed that the changes in A-FABP were independently and positively associated with changes in NT-proBNP after adjusting for confounding factors (β = 0.320, P = 0.007).. Rosiglitazone-mediated increase of A-FABP is closely associated with the elevation of NT-proBNP, a well-established marker of cardiac dysfunction. The findings of our study imply that A-FABP may mediate the cross-talk between heart and adipose tissue.

Topics: Adult; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Fatty Acid-Binding Proteins; Female; Humans; Hypoglycemic Agents; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Receptor Cross-Talk; Rosiglitazone; Thiazolidinediones

Baseline levels of N-terminal fragment of the brain natriuretic peptide prohormone (NT-pro-BNP) are associated with myocardial ischemia in non-diabetic patients with stable angina pectoris. A total of 281 patients with diabetes mellitus type 2 and stable angina pectoris underwent myocardial perfusion scintigraphy (MPS). Myocardial ischemia on MPS was present in 140 (50%) patients. These ischemic patients had significantly higher NT-pro-BNP levels compared with patients without ischemia: 183 pg/ml (64-324 pg/ml) vs. 88 pg/ml (34-207 pg/ml), respectively (p<0.001). In addition, NT-pro-BNP ≥180 pg/ml was an independent predictor of the presence of myocardial ischemia (OR 2.36, 95%CI 1.40-3.97, p=0.001). Possible confounding factors such as age and creatinine clearance were of no influence on the predictive value in this specific patient population. These findings strengthen the idea that NT-pro-BNP may be of value in the early detection of diabetic patients with hemodynamic significant coronary artery disease.

Topics: Aged; Biomarkers; Diabetes Mellitus, Type 2; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Protein Precursors

Glitazones are powerful insulin sensitisers prescribed for the treatment of type 2 diabetes. Their use is, however, associated with fluid retention and an increased risk of congestive heart failure. We previously demonstrated that pioglitazone increases proximal sodium reabsorption in healthy volunteers. This study examines the effects of pioglitazone on renal sodium handling in individuals prone to insulin resistance, i.e. those with diabetes and/or hypertension.. In this double-blind randomised placebo-controlled four-way crossover study, we examined the effects of pioglitazone (45 mg daily during 6 weeks) or placebo on renal, systemic and hormonal responses to changes in sodium intake in 16 individuals, eight with type 2 diabetes and eight with hypertension.. Pioglitazone was associated with a rapid increase in body weight and an increase in diurnal proximal sodium reabsorption, without any change in renal haemodynamics or in the modulation of the renin-angiotensin aldosterone system to changes in salt intake. A compensatory increase in brain natriuretic peptide levels was observed. In spite of sodium retention, pioglitazone dissociated the blood-pressure response to salt and abolished salt sensitivity in salt-sensitive individuals.. Pioglitazone increases diurnal proximal sodium retention in diabetic and hypertensive individuals. These effects cause fluid retention and may contribute to the increased incidence of congestive heart failure with glitazones.. ClinicalTrial.gov NCT01090752. Hypertension Research Foundation Lausanne.

Topics: Analysis of Variance; Blood Pressure; Body Weight; Cross-Over Studies; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Humans; Hypertension; Hypoglycemic Agents; Insulin Resistance; Male; Metformin; Natriuretic Peptide, Brain; Pioglitazone; Sodium, Dietary; Thiazolidinediones

Low 25-hydroxyvitamin D levels predict future cardiovascular events and are common in patients with type 2 diabetes. We compared the effect of 100,000 and 200,000 IU doses of vitamin D(3) on endothelial function, blood pressure and markers of glycaemic control in patients with type 2 diabetes.. This was a randomised, parallel group, placebo-controlled trial. Patients with type 2 diabetes and baseline 25-hydroxyvitamin D levels <100 nmol/l were enrolled from community and hospital-based diabetes clinics. Participants were assessed in a university department of clinical pharmacology and received a single oral dose of placebo or vitamin D(3) (100,000 IU or 200,000 IU) at baseline, randomly allocated via numbered bottles prepared offsite; participants and investigators were both blinded to treatment allocation. Endothelial function, office blood pressure, B-type natriuretic peptide, insulin resistance and glycosylated haemoglobin were measured at baseline, and at 8 and 16 weeks.. We randomised 61 participants to the three groups (placebo 22, 100,000 IU vitamin D(3) 19, 200,000 IU vitamin D(3) 20). There was no significant difference in the primary outcome of endothelial function at 8 weeks (placebo 5.2%, n = 22; 100,000 IU 4.3%, n = 19; 200,000 IU 4.9%, n = 17) or at 16 weeks. Insulin resistance and glycosylated haemoglobin did not improve with either dose of vitamin D(3). On covariate analysis, systolic blood pressure was significantly lower in both treatment arms than in the placebo group at 8 weeks (placebo 146.4 mmHg, 100,000 IU 141.4 mmHg [p = 0.04 vs placebo], 200,000 IU 136.8 mmHg [p = 0.03 vs placebo]). B-type natriuretic peptide levels were significantly lower in the 200,000 IU group by 16 weeks (placebo 34 pg/ml, 200,000 IU 21 pg/ml, p = 0.02). No significant excess of adverse effects was noted in the treatment arms.. High-dose vitamin D(3) improved systolic blood pressure and B-type natriuretic peptide levels, but not endothelial function, insulin resistance or glycosylated haemoglobin in patients with type 2 diabetes.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Blood Glucose; Blood Pressure; Cholecalciferol; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Double-Blind Method; Endothelium, Vascular; Enzyme-Linked Immunosorbent Assay; Female; Glycated Hemoglobin; Humans; Insulin Resistance; Male; Middle Aged; Natriuretic Peptide, Brain; Treatment Outcome

N-terminal-pro-B-type-natriuretic-peptide (NT-pro-BNP) concentrations are altered in renal failure. This study examined the effect of baseline and change from baseline NT-pro-BNP on cardiovascular outcome and mortality in haemodialysis patients.. On the basis of the German Diabetes and Dialysis Study, which evaluated atorvastatin in 1255 type 2 diabetes mellitus (T2DM) haemodialysis patients (median follow-up 4 years), the impact of NT-pro-BNP on pre-specified, adjudicated endpoints was investigated: sudden death (SD; n = 160), stroke (n = 99), myocardial infarction (MI; n = 200), cardiovascular events (CVEs: cardiac death, MI, stroke; n = 465), all-cause mortality (n = 612). Patients with baseline NT-pro-BNP ≥ 9252 pg/mL (fourth quartile) exhibited a more than four-fold risk of stroke [hazard ratio (HR) 4.1; 95% confidence interval (CI) 2.0-8.4] and a more than two-fold risk of SD (HR 2.0; 95% CI 1.2-3.3), CVE (HR 2.0; 95% CI 1.5-2.7), and mortality (HR 2.1; 95% CI 1.6-2.7) compared with patients with baseline NT-pro-BNP ≤ 1433 pg/mL (first quartile). Change in NT-pro-BNP was strongly associated with SD, CVE, and mortality. Doubling of NT-pro-BNP increased the risk of death by 46% (95% CI 1.1-2.0). Neither baseline nor change in NT-pro-BNP was significantly associated with MI.. Increasing NT-pro-BNP is a risk factor for SD, CVE, and mortality in haemodialysis patients with T2DM. Whether NT-pro-BNP-guided treatment improves outcome needs to be evaluated prospectively.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Death, Sudden, Cardiac; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Double-Blind Method; Female; Germany; Humans; Kaplan-Meier Estimate; Male; Myocardial Infarction; Natriuretic Peptide, Brain; Peptide Fragments; Renal Dialysis; Risk Factors; Stroke; Treatment Outcome; Young Adult

This study was aimed to compare the effect of insulin plus rosiglitazone with that of insulin plus metformin on the level of serum N-terminal pro-brain natriuretic peptide (NT-BNP) in patients with type 2 diabetes mellitus, and to find out whether serum NT-BNP can be used as an index for predicting heart failure induced by rosiglitazone in the cases of type 2 diabetes mellitus. Sixty type 2 diabetic patients were recruited and were randomly divided into two groups: group A (n = 30) received insulin plus rosiglitazone (4 mg/d) and group B (n = 30) received insulin plus metformin. The observations covered an 8-weeks' course of treatment. Serum NT-BNP was measured at the beginning and at the end of 8 weeks. The Before-After study revealed that the level of serum NT-BNP did not change apparently in the two groups (P >0.05). There was no remarkable difference in the level of serum NT-BNP between the two groups (P>0.05). There were 3 cases with edema in the group of insulin plus rosiglitazone, but none with heart failure; in these three cases, the mean serum NT-BNP level at the end of the treatment exhibited an increase of 108.99 fmol/ml when compared with that at the beginning. Neither insulin plus rosiglitazone nor insulin plus metformin had apparent effect on the level of serum NT-BNP in the patients with type 2 diabetes mellitus. The question of whether serum NT-BNP is a predictive index of heart failure awaits answers given by more observation on type 2 diabetes mellitus patients using rosiglitazone.

Topics: Aged; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Humans; Hypoglycemic Agents; Insulin; Male; Metformin; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Rosiglitazone; Thiazolidinediones

Aldosterone antagonism improves endothelial function (and reduces deaths) in chronic heart failure. It is not known whether similar effects occur in other high-risk groups such as patients with diabetes and hypertension. We therefore assessed the full effects of aldosterone blockade in poorly controlled hypertensive patients with type 2 diabetes, focussing on blood pressure, endothelial function, glycaemic control and key hormones.. We performed a randomised, placebo-controlled, double-blind, crossover study on 50 patients with type 2 diabetes and treated but poorly controlled hypertension, comparing spironolactone versus placebo. Patients had their endothelial function assessed by standard forearm venous occlusion plethysmography.. There was no significant improvement in endothelium-dependent vasodilatation in response to acetylcholine, despite highly significant reductions in systolic and diastolic blood pressure. However, spironolactone significantly worsened glycaemic control, plasma angiotensin II and cortisol.. Spironolactone is highly effective in lowering blood pressure in patients with type 2 diabetes and poorly controlled hypertension on standard treatment, but does not improve vascular endothelial function in this group. We speculate that any tendency for the spironolactone-induced lowering of blood pressure to improve endothelial function is offset by its tendency to worsen glycaemic control and increase the levels of angiotensin II and even possibly cortisol.

Topics: Aged; Aldosterone; Angiotensin II; Blood Glucose; Blood Pressure; Body Mass Index; Cross-Over Studies; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Double-Blind Method; Endothelium, Vascular; Female; Fibroblast Growth Factors; Glycated Hemoglobin; Humans; Hydrocortisone; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain

We attempted to test the hypothesis that chronic angiotensin II type 1A receptor blockade (ARB) alters myocardial collagen turnover leading to an improvement of diastolic dysfunction in diabetic patients.. Forty-eight type 2 diabetic patients were divided into 2 groups: 38 treated with candesartan for 6 months, and 10 without candesartan, as controls. Doppler mitral flow velocity pattern and biomarkers of collagen type I turnover were assessed before and after ARB during a 6-month period. The mitral E/A ratio increased from 0.65+/-0.11 to 0.75+/-0.19. The carboxy-terminal propeptide of procollagen type I (PIP), an index of collagen type I synthesis, decreased and the carboxy-terminal telopeptide of collagen type I (CITP), an index of collagen type I degradation, increased following ARB. Consequently, the PIP/CITP ratio, an index of coupling between the synthesis and degradation of collagen type I, decreased. None of the indexes changed in the control group. The change in left ventricular chamber stiffness did not correlate with the change in PICP (r=0.08, p=NS), but it did with the changes in CITP or in the PIP/CITP ratio (r=0.35, p<0.05; r=0.39, p<0.05).. Chronic ARB improves diastolic dysfunction in diabetic patients, at least partially through the attenuation of myocardial fibrosis, by regulating collagen turnover, particularly by facilitating collagen degradation.

Topics: Aged; Angiotensin II Type 1 Receptor Blockers; Benzimidazoles; Biphenyl Compounds; Blood Pressure; Collagen; Diabetes Mellitus, Type 2; Endomyocardial Fibrosis; Female; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Receptor, Angiotensin, Type 1; Renin-Angiotensin System; Tetrazoles; Ventricular Dysfunction, Left

Thiazolidinediones (TZD) have become a powerful tool for lowering insulin resistance. The problem of cardiovascular adverse events including fluid retention and risk of heart failure should be well known and recognised. We aimed to evaluate the long-term effects of rosiglitazone on cardiac function and fluid dynamics. Forty-six type 2 diabetic patients were randomised to treatment with rosiglitazone or metformin or to a control group. There are no significant differences between the groups in the duration of diabetes, HbA1c, plasma brain natriuretic peptide (BNP) levels, body mass index and myocardial performance indexes (MPIs) before the treatment. After three and six months all these parameters were repeated. Rosiglitazone increased plasma BNP levels and worsened MPIs 3 months after the start of treatment. Also left ventricular end-systolic volume increased and weight gain was observed. But these results were statistically non-significant (all p>0.05). When we continued rosiglitazone treatment to six months the increase in BNP levels became soft and statistically significant improvements were seen in MPIs (p<0.01). Also left ventricular end-systolic volume decreased significantly (p=0.004) and weight gain was stopped. In patients with type 2 diabetes, TZD treatment might have slight adverse effects on ventricular contractility and fluid dynamics at the beginning of the therapy. However, these changes seem to stabilise in the long term.

Topics: Aged; Blood Glucose; Cholesterol; Diabetes Mellitus, Type 2; Echocardiography; Female; Glycated Hemoglobin; Heart; Heart Function Tests; Humans; Hypoglycemic Agents; Male; Middle Aged; Natriuretic Peptide, Brain; Rosiglitazone; Thiazolidinediones; Ventricular Function, Left

Adiponectin, an adipocyte-derived hormone, has been shown to prevent the progression of left ventricular hypertrophy (LVH). However, recent studies have demonstrated increased levels of adiponectin according to the severity of chronic heart failure. We therefore investigated the relationships between adiponectin, brain natriuretic peptide (BNP), and LVH in type 2 diabetic patients on hemodialysis.. The study population comprised 41 type 2 diabetic patients on hemodialysis. Left ventricular mass index (LVMI) and criteria for LVH were determined on the basis of echocardiographic findings. Serum adiponectin and plasma BNP levels were assayed with a commercially available kit.. Serum adiponectin levels significantly correlated with BMI (r = -0.49, p < 0.01), HDL-C (r = 0.36, p < 0.05) and TG (r = -0.49, p < 0.01). In addition, serum adiponectin levels correlated significantly and positively with plasma BNP levels (r = 0.36, p < 0.05). This relationship remained significant after adjustment for age, gender, and BMI (r = 0.34, p < 0.05). Serum adiponectin levels as well as plasma BNP levels were significantly higher than in patients without LVH (p < 0.05; p < 0.01, respectively), accompanied by a positive correlation between these levels and LVMI (r = 0.42, p < 0.01; r = 0.32, p < 0.05, respectively).. Increased levels of adiponectin were associated with elevated BNP levels and LVH in hemodialysis patients with type 2 diabetes mellitus. It is speculated that adiponectin levels may be modulated by chronic hypervolemic state in this population.

Topics: Adiponectin; Biomarkers; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Female; Humans; Hypertrophy, Left Ventricular; Male; Middle Aged; Natriuretic Peptide, Brain; Renal Dialysis

In this study we evaluated the effect of a dual blockade with enalapril and losartan on the reduction of overt macroproteinuria and its potential mechanism(s) in hypertensive patients with type 2 diabetes. Twenty-six hypertensive patients with type 2 diabetes at the baseline were administered 5 mg of enalapril once daily for 12 weeks. At the beginning of the study, the subjects were assigned to receive an add-on of 50 mg of losartan once daily or 5 mg of enalapril once daily for another 12 weeks. Blood samples were collected at the baseline, at the beginning, and at the end of the study for the measurement of laboratory parameters, and these data, including blood pressure, were compared between the two groups. Treatment with 5 mg of enalapril significantly decreased the systolic blood pressure level in both groups, and the addition of losartan and/or enalapril further decreased the levels. There was no difference in blood pressure between the two groups. However, the addition of losartan, but not enalapril, significantly decreased the urinary protein excretion level, plasma aldosterone, and hypersensitive-C-reactive protein at the end of the study. The results established that the dual blockade of angiotensin II with enalapril and losartan has a greater clinical benefit for high-risk patients with hypertension and advanced diabetic nephropathy.

Topics: Aged; Aldosterone; Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; C-Reactive Protein; Cystatin C; Cystatins; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Enalapril; Female; Humans; Hypertension; Losartan; Male; Middle Aged; Natriuretic Peptide, Brain; Proteinuria; Transforming Growth Factor beta

To examine pioglitazone as add-on to metformin and insulin secretagogues in patients with type 2 diabetes and inadequate glycaemic control and its effect on glycaemic control, surrogate measures of insulin sensitivity (adiponectin) and beta-cell function (proinsulin/insulin) and fluid retention.. Prospective open-label study of 54 patients with type 2 diabetes and HbA1c>or=6.5% admitted to outpatient unit at Malmö University Hospital. The patients received 30-45 mg pioglitazone daily during 26 weeks in addition to their existing antidiabetic medication. After 26 weeks, one-third of patients were followed for 3 months without pioglitazone.. HbA1c decreased (7.8+/-0.9-6.3+/-0.9%, P<0.001) with 61% of patients achieving levels<6.5%. However, in the group followed for another 3 months HbA1c increased (6.1+/-0.73-7.1+/-0.9, n=18, P<0.001) after pioglitazone withdrawal. Adiponectin increased (6.1+/-2.8-13.2+/-5.8 microg mL-1, P<0.001) and the proinsulin to insulin ratio decreased (0.89+/-0.66-0.66+/-0.53, P<0.001). Nt-proBNP increased from 487.3+/-252.2 to 657.8+/-392.1 pmol L-1 (P<0.001).. Pioglitazone is effective in achieving glycaemic targets and reducing risk factors involved in atherosclerosis and improving beta-cell function when used as part of triple oral therapy in patients with type 2 diabetes and secondary drug failure. Nt-proBNP increase with concomitant decrease in haemoglobin suggests a subclinical sign of fluid retention.

Topics: Adiponectin; Administration, Oral; Aged; Biomarkers; Blood Glucose; Case-Control Studies; Cystatin C; Cystatins; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Glyburide; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Male; Metformin; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Pioglitazone; Proinsulin; Prospective Studies; Statistics, Nonparametric; Thiazolidinediones

Diabetes has been implicated in reduced myocardial compliance and changes in the intercellular matrix of the myocardium. We determined the effect of diabetes on B-type natriuretic peptide (BNP) concentrations in patients presenting to the emergency department with dyspnea.. The Breathing Not Properly Multinational Study was a prospective evaluation of 1,586 patients. A subset of 922 patients was obtained and subdivided into the following groups: group 1 (n = 324), neither diabetes nor heart failure; group 2 (n = 107), diabetes and no heart failure; group 3 (n = 247), no diabetes and heart failure; group 4 (n = 183), both diabetes and heart failure; group 5 (n = 41), heart failure history with no diabetes; and group 6 (n = 20), heart failure history with diabetes. Patients from groups 1, 3, and 5 were matched to groups 2, 4, and 6, respectively, to have the same mean age, sex distribution, BMI, renal function, and New York Heart Association (NYHA) classification (for heart failure).. There was no significant difference in median BNP levels between diabetes and no diabetes among no heart failure patients (32.4 vs.32.9 pg/ml), heart failure patients (587 vs. 494 pg/ml), and those with a heart failure history (180 vs. 120 pg/ml). Receiver-operating characteristic curve analysis of the area under the curve for BNP was not different in diabetic versus nondiabetic patients (0.888 vs. 0.878, respectively). However, in a multivariate model, diabetes was an independent predictor of a final diagnosis of heart failure (odds ratio 1.51, 95% CI 1.03-2.02; P < 0.05).. History of diabetes does not impact BNP levels measured in patients with acute dyspnea in the emergency department. Despite the impact of diabetes on the cardiovascular system, diabetes does not appear to confound BNP levels in the emergency department diagnosis of heart failure.

Topics: Acute Disease; Age Factors; Area Under Curve; Biomarkers; Confidence Intervals; Diabetes Mellitus, Type 2; Dyspnea; Emergency Service, Hospital; Female; Heart Failure; Humans; Male; Multivariate Analysis; Natriuretic Peptide, Brain; Probability; Prognosis; Prospective Studies; Reference Values; Risk Assessment; Sensitivity and Specificity; Severity of Illness Index; Sex Factors

We monitored the change in plasma ANP and BNP levels (as markers for left ventricular dysfunction (LVD)) in DM2 patients treated with pioglitazone (Pio) for 4 weeks. Thirty DM2 patients with no sign of heart failure were treated with Pio (15 mg/day), and their plasma ANP (normal levels

Topics: Aged; Atrial Natriuretic Factor; Body Mass Index; Buformin; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Heart Failure; Humans; Hypoglycemic Agents; Male; Middle Aged; Natriuretic Peptide, Brain; Pioglitazone; Stroke Volume; Thiazoles; Thiazolidinediones

This study sought to determine if the severity of autonomic perturbations in patients with heart failure are affected by the presence of diabetes. Decreased HRV is frequent in diabetic patients free of clinically apparent heart disease and has been invoked as a risk factor for sudden cardiac death. However, reduced HRV is also commonly present in patients with left ventricular dysfunction. The effect of diabetes on autonomic dysfunction in this setting is not known. Holter ECGs from 69 diabetic patients and 85 nondiabetic control subjects with heart failure were analyzed. The severity of autonomic dysfunction was assessed using 24-hour time- and frequency-domain HRV analysis. Prognostically important time- and frequency-domain HRV measures (SDNN, SDANN5, total power, and ultra-low frequency power) were not different between the two groups. Time- and frequency-domain parameters modulated by parasympathetic tone (pNN50, RMSSD, and HF power) were depressed to a similar degree in the diabetic and the nondiabetic groups. The low frequency power was significantly lower in diabetic patients (5.8 +/- 0.7 vs 5.3 +/- 1.0, P = 0.02). The ratio of low to high frequency power was substantially lower in the diabetic group (2.2 +/- 0.2 vs 1.4 +/- 0.2, P < 0.0001). These differences were more apparent in insulin-treated diabetics. In the presence of heart failure, HRV parameters that are most predictive of adverse outcome are similar in diabetic and nondiabetic patients. Furthermore, during increased sympathetic stimulation in the setting of heart failure, diabetes does not worsen parasympathetic withdrawal but may mitigate sympathetic activation.

Topics: Atrial Natriuretic Factor; Cardiotonic Agents; Case-Control Studies; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Dobutamine; Electrocardiography, Ambulatory; Female; Heart Failure; Heart Rate; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Signal Processing, Computer-Assisted

Measurement of natriuretic peptides (NPs) has proven its clinical value as biomarker, especially in the context of heart failure (HF). In contrast, a state of partial NP deficiency appears integral to several conditions in which lower NP concentrations in plasma presage overt cardiometabolic disease. Here, obesity and type 2 diabetes have attracted considerable attention. Other factors-including age, sex, race, genetics, and diurnal regulation-affect the NP "armory" and may leave some individuals more prone to development of cardiovascular disease. The molecular maturation of NPs has also proven complex, with highly variable O-glycosylation within the biosynthetic precursors. The relevance of this regulatory step in post-translational propeptide maturation has recently become recognized in biomarker measurement/interpretation and cardiovascular pathophysiology. An important proportion of people appear to have reduced effective net NP bioactivity in terms of receptor activation and physiological effects. The state of NP deficiency both entails a potential for further biomarker development and could also offer novel pharmacological possibilities. Alleviating the state of NP deficiency before development of overt cardiometabolic disease in selected patients could be a future path for improving precision medicine.

Topics: Atrial Natriuretic Factor; Biomarkers; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Humans; Natriuretic Peptide, Brain; Natriuretic Peptides

Diabetic kidney disease (DKD) is the most common cause of end-stage kidney disease (ESKD). The identification of risk factors involved in the progression of DKD to ESKD is expected to result in early detection and appropriate intervention and improve prognosis. This study aimed to explore whether plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) was associated with kidney outcomes in patients with type 2 diabetes mellitus (T2DM) and biopsy-proven DKD.. Patients with biopsy-proven DKD who were followed up at West China Hospital over 12 months were enrolled. The kidney outcome was defined as progression to ESKD. The cutoff value of plasma NT-proBNP concentration was calculated by using receiver operating characteristic (ROC) curve analysis. The influence of NT-proBNP levels on kidney outcome in patients with DKD was assessed using Cox regression analysis.. A total of 30 (24.5%) patients reached ESKD during a median follow-up of 24.1 months. The baseline serum NT-proBNP level had a significant correlation with baseline proteinuria, kidney function, glomerular lesions, interstitial fibrosis tubular atrophy (IFTA), and arteriolar hyalinosis. Multivariate Cox regression analysis indicated that increased NT-proBNP level was significantly associated with a higher risk of progression to ESKD (HR 6.43; 95% CI (1.65-25.10,. A higher level of plasma NT-proBNP predicts kidney prognosis in patients with biopsy-proven DKD. This warrants further investigation into the potential mechanisms.

Topics: Biomarkers; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Disease Progression; Humans; Kidney Failure, Chronic; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis

Topics: Biomarkers; Diabetes Mellitus, Type 2; Heart Failure; Humans; Natriuretic Peptide, Brain; Natriuretic Peptides; United States; Vasodilator Agents

International guidelines recommend natriuretic peptide biomarker-based screening for patients at high heart failure (HF) risk to allow early detection. There have been few reports about the incorporation of screening procedure to existing clinical practice.. To implement screening of left ventricular dysfunction in patients with type 2 diabetes mellitus (DM).. A prospective screening study at the DM complication screening centre was performed.. Between 2018 and 2019, 1043 patients (age: 63.7±12.4 years; male: 56.3%) with mean glycated haemoglobin of 7.25%±1.34% were recruited. 81.8% patients had concomitant hypertension, 31.1% had coronary artery disease, 8.0% had previous stroke, 5.5% had peripheral artery disease and 30.7% had chronic kidney disease (CKD) stages 3-5. 43 patients (4.1%) had an elevated N-terminal prohormone of brain natriuretic peptide (NT-proBNP) concentration above the age-specific diagnostic thresholds for HF, and 43 patients (4.1%) had newly detected atrial fibrillation (AF). The prevalence of elevated NT-proBNP increased with age from 0.85% in patients aged <50 years to 7.14% in those aged 70-79 years and worsening kidney function from 0.43% in patients with CKD stage 1 to 42.86% in CKD stage 5. In multivariate logistic regression, male gender (OR: 3.67 (1.47-9.16), p = 0.005*), prior stroke (OR: 3.26 (1.38-7.69), p = 0.007*), CKD (p<0.001*) and newly detected AF (OR: 7.02 (2.65-18.57), p<0.001*) were significantly associated with elevated NT-proBNP. Among patients with elevated NT-proBNP, their mean left ventricular ejection fraction (LVEF) was 51.4%±14.7%, and 45% patients had an LVEF <50%.. NT-proBNP and ECG screening could be implemented with relative ease to facilitate early detection of cardiovascular complication and improve long-term outcomes.

Topics: Aged; Atrial Fibrillation; Biomarkers; Diabetes Mellitus, Type 2; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Renal Insufficiency, Chronic; Stroke; Stroke Volume; Ventricular Dysfunction, Left; Ventricular Function, Left

Heart failure (HF) is a chronic disease that causes approximately 300,000 and 250,000 deaths per year in Europe and United States, respectively. Type 2 Diabetes Mellitus (T2DM) is one the major risk factors of HF, and the investigation of NT-proBNP might support the early identification of HF in T2DM sufferers. Nevertheless, this parameter is poorly investigated. Thus, we aimed to demographically and clinically characterize diabetic patients which were prescribed with NT-proBNP in the primary care setting.. Using a primary care database, we formed a cohort of patients aged ≥18 years diagnosed with T2DM between 2002 and 2021. A multivariate Cox model was adopted to assess the determinants associated with the prescription of NT-proBNP.. Among 167,961 T2DM patients, 7558 (4.5%, 95% CI: 4.4-4.6) were prescribed with NT-proBNP. Males and increasing age were expectedly associated with a higher propensity to be prescribed with NT-proBNP. In addition, a significant association was found for those suffering from obesity, ischemic cardiomyopathy, stroke, atrial fibrillation, hypertension, and with a Charlson Index of 2+.. These determinants might contribute to investigate the NT-proBNP in T2DM sufferers. A decision support system to appropriately ease the prescription of NT-proBNP might be therefore implemented in primary care settings.

Topics: Adolescent; Adult; Biomarkers; Diabetes Mellitus, Type 2; Heart Failure; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis

FGF23 (fibroblast growth factor 23) is associated with a higher mortality risk in type 2 diabetes, but the mechanism is unclear. We aimed to study whether NT-proBNP (N-terminal pro-brain natriuretic peptide) mediates the association between FGF23 and mortality.. We analyzed C-terminal FGF23 and NT-proBNP levels in 399 patients with type 2 diabetes. Cox regression analyses were performed, followed by mediation analyses using Structural Equation Modeling. During follow-up of 9.2 [7.6-11.3] years, 117 individuals died. FGF23 was associated with all-cause mortality, independent of potential confounders (fully adjusted hazard ratio [HR], 2.32 [95% CI, 1.21-4.43],. These findings suggest that a higher FGF23 level is associated with increased mortality in individuals with type 2 diabetes through an effect on volume homeostasis.

Topics: Biomarkers; Diabetes Mellitus, Type 2; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis

There is little evidence on the use of sodium-glucose cotransporter 2 (SGLT2) inhibitors in older patients with heart failure. This work analyzed the clinical efficacy and safety of empagliflozin continuation in very old patients with type 2 diabetes hospitalized for acute decompensated heart failure.. We conducted a real-world observational study between September 2015 and June 2021. Patients ≥80 years were grouped by antihyperglycemic regimen: (1) continuation of preadmission empagliflozin combined with basal insulin regimen and (2) conventional basal-bolus insulin regimen. A propensity score matching analysis matched patients in both groups in a 1:1 manner. The primary outcome was differences in clinical efficacy measured by the visual analogue scale dyspnea score, NT-proBNP levels, diuretic response, and cumulative urine output. Safety endpoints such as adverse events, worsening heart failure, discontinuation of empagliflozin, length of hospital stay, and in-hospital deaths were also analyzed.. After propensity score matching, 79 patients were included in each group. At discharge, the N-terminal pro-brain natriuretic peptide (NT-proBNP) levels were lower in the empagliflozin continuation group than in the insulin group (1699 ± 522 vs. 2303 ± 598 pg/ml, p = 0.021). Both the diuretic response and cumulative urine output were greater in patients treated with empagliflozin than in patients with basal-bolus insulin during the hospitalization (at discharge: -0.14 ± -0.06 vs. -0.24 ± -0.10, p = 0.044; and 16,100 ± 1510 vs. 13,900 ± 1220 ml, p = 0.037, respectively). No differences were observed in safety outcomes.. In very old patients with type 2 diabetes hospitalized for acute heart failure, continuing preadmission empagliflozin reduced NT-proBNP levels and increased diuretic response and urine output compared to a basal-bolus insulin regimen. The empagliflozin regimen also showed a good safety profile.

Topics: Aged; Benzhydryl Compounds; Diabetes Mellitus, Type 2; Diuretics; Glucosides; Heart Failure; Hospitalization; Humans; Insulins; Natriuretic Peptide, Brain; Peptide Fragments; Sodium-Glucose Transporter 2 Inhibitors

Topics: Canagliflozin; Diabetes Mellitus, Type 2; Heart Failure; Humans; Natriuretic Peptide, Brain; Natriuretic Peptides; Sodium-Glucose Transporter 2 Inhibitors

Topics: Arteries; Blood Pressure; Diabetes Mellitus, Type 2; Heart Ventricles; Humans; Natriuretic Peptide, Brain

In patients with type 2 diabetes mellitus (T2DM) without known cardiovascular disease, the association between B-type natriuretic peptide (BNP) and cardiovascular events except for heart failure has not been elucidated. We aimed to investigate this association in high-risk T2DM patients.. We analyzed the association between BNP and cardiovascular events, including coronary, cerebral, renal, and vascular events or cardiovascular death based on the single and serial measurement of BNP in T2DM patients with retinopathy and hyperlipidemia without known cardiovascular disease enrolled in the EMPATHY study.. Data from 4966 patients were analyzed for baseline BNP analysis. The median BNP value was 15.0 pg/mL. When analyzed in quartiles of baseline BNP (interquartile range 7.5-29.2 pg/mL), Q2, Q3, and Q4 were associated with cardiovascular events compared with Q1 (hazard ratio [HR]: Q2, 1.91 [P = 0.003]; Q3, 1.63 [P = 0.031]; Q4, 3.20 [P < 0.001]). The analysis of 12-month BNP showed similar associations. In serial BNP measurement, compared with low-low BNP group (baseline ≤35 pg/mL and 12-month ≤35 pg/mL), low-high BNP group as well as high-high BNP group was associated with cardiovascular events (HR: low-high, 2.05 [P = 0.004]; high-high, 2.07 [P = 0.001]) and non-renal cardiovascular events. High-low BNP group tended to be associated with non-renal cardiovascular events (HR vs low-low: 2.05 [P = 0.056]).. BNP levels were associated with first cardiovascular events except for heart failure in T2DM patients with retinopathy and hyperlipidemia. Serial BNP measurement may be useful in further stratifying high-risk patients among this T2DM population.

Topics: Biomarkers; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Heart Failure; Humans; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; Retinal Diseases

Background Baseline and temporal changes in natriuretic peptide (NP) concentrations have strong prognostic value with regard to long-term cardiovascular risk stratification. To increase the clinical utility of NP sampling for patient management, we wanted to assess the incremental predictive value of 2 serial NP measurements compared with a single measurement and provide absolute risk estimates for cardiovascular death or heart failure hospitalization (HFH) within 6 months based on 2 serial NP measurements. Methods and Results Consecutive NP samples obtained from 5393 patients with a recent coronary event and type 2 diabetes enrolled in the ELIXA (Evaluation of Cardiovascular Outcomes in Patients With Type 2 Diabetes After Acute Coronary Syndrome During Treatment With Lixisenatide) trial were used to construct best logistic regression models with outcome of cardiovascular death or HFH (136 events). Absolute risk estimates of cardiovascular death or HFH within 6 months using either BNP (B-type natriuretic peptide) or NT-proBNP (N-terminal pro-BNP) serial measurements were depicted based on the concentrations of 2 serial NP measurements. During the 6-month follow-up periods, the incidence rate (±95% CIs) of cardiovascular death or HFH for patients was 14.0 (11.8‒16.6) per 1000 patient-years. Risk prediction depended on NP concentrations from both prior and current sampling. NP sampling 6 months apart improved the predictive value and reclassification of patients compared with a single sample (AUROC [Area Under the Receiver Operating Characteristic curve]: BNP,

Topics: Biomarkers; Coronary Artery Disease; Diabetes Mellitus, Type 2; Heart Failure; Hospitalization; Humans; Natriuretic Peptide, Brain; Natriuretic Peptides; Peptide Fragments; Predictive Value of Tests; Prognosis; Vasodilator Agents

Diabetes mellitus is a global health problem. Cardiovascular events accounts for approximately 50 percent of mortality amongst the diabetics. Diabetics often present with silent myocardial ischaemia, since myocardial ischaemia is a strong trigger of N-terminal pro-B-type natriuretic peptide (NT-proBNP) release, we hypothesized that NT-proBNP might be useful in the early diagnosis. This study also evaluates whether any correlation exits between NT-proBNP levels and myocardial performance index (MPI).. This case control study was done on 30 patients with type 2 diabetes and similar matched group of 30 controls. Investigations like fasting and postprandial sugar level, kidney function test, HBA1c, lipid profile and NT-ProBNP levels were done. TMT was done to diagnose silent MI. Echocardiography was performed to assess MPI. The outcome measures were cut off levels of NT-ProBNP for predicting silent myocardial ischaemia based on TMT. P<0.05 was considered as significant.. NT-proBNP (pg/mL) was significantly increased in Diabetics in comparison to controls (595.33±464.48 vs 110.97 ± 34.81, p <.0001). MPI was significantly higher in diabetics (0.54±0.08 vs 0.33±0.02, p<.0001), and NT-proBNP showed significant positive correlation myocardial performance index (r= 0.726, p<0.0001). Silent MI was seen in 18(60%) patients which was based on TMT testing. Compared to those without silent MI, patients with silent MI had higher NTproBNP levels (795.5 vs 106, p value=0.0001) and higher MPI (0.59 ± 0.06 vs 0.46 ± 0.05, p value<.0001). A cut off of NT-pro BNP(pg/ mL) of >152 predicted silent MI in 93.33% cases with 100% sensitivity, 83.33% specificity, 90% PPV and 100% NPV.. NT-proBNP is a novel marker with positive correlation with MPI. It may be used as an independent predictor for silent MI in diabetics, thereby helping in reduction and treatment of CVD among them. Thus, it is suggested to screen all asymptomatic diabetics for underlying myocardial ischaemia by MPI, preferably, or by NTproBNP levels.

Topics: Biomarkers; Case-Control Studies; Coronary Artery Disease; Diabetes Mellitus, Type 2; Humans; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments

The aim: To investigate the level of B-type natriuretic peptide (BNP) and to establish its relationship with structural and functional indicators of the myocardium in patients having acute myocardial infarction (AMI), which is complicated by heart failure (HF) with concomitant type 2 diabetes mellitus (DM2).. Materials and methods: The study included 120 patients who were grouped by clinical diagnosis. Every patient underwent transthoracic echocardiography of the heart: left ventricular (LV) ejection fraction (EF), left ventricular myocardial mass index (LVMI), LV relative wall thickness (LVWT), BNP, HbA1c.. Results: LV EF was statistically significantly lower in group 2 compared with group 1. A significant difference was found. Significant difference between LVWT within indicators of groups 1 and 2 was found. There was a statistically significant increase of the LVMI in group 2 compared to group 1. Against the background of AMI, the formation of eccentric LVH prevailed in 61% cases. There was a statistically significant increase in BNP within the group of patients suffering of AMI with HF and concomitant DM2.. Conclusions: There was found a statistically significant increase in BNP in patients suffering of AMI with HF and concomitant DM2, which indicates a significant degree of damage to cardiomyocytes and causes an aggravating course of HF. The relationship between BNP and LV EF was revealed , which can be used to prognostic the severity of HF in this category of patients. A strong correlation between BNP and HbA1 was discovered, which indicates a burdensome unity of metabolic disorders that accelerate the development and progression of HF.

Topics: Biomarkers; Diabetes Mellitus, Type 2; Echocardiography; Heart Failure; Humans; Myocardial Infarction; Natriuretic Peptide, Brain

Topics: Diabetes Mellitus, Type 2; Glyceraldehyde; Heart Failure; Humans; Natriuretic Peptide, Brain; Stroke Volume; Tumor Necrosis Factor-alpha; Ventricular Function, Left; Ventricular Remodeling

Cardiovascular disease (CVD) is a leading cause of death in both men and women. Type 1 and 2 diabetes mellitus (DM1 and DM2) are well-known risk factors for CVD. In addition, gestational diabetes mellitus (GDM) is a female sex-specific risk factor for CVD. Here, we measure circulating concentrations of cardiac troponin T (cTNT), N-terminal pro-B-type natriuretic peptide (NT-proBNP) and growth differentiation factor 15 (GDF-15) during pregnancy-a window of time often referred to as a cardiovascular stress test for women.. This study utilized data from 384 pregnant women: 64 with DM1, 16 with DM2, 35 with GDM and 269 euglycemic controls. Blood was predominantly sampled within a week before delivery. Cardiovascular biomarker concentrations were measured in serum using electrochemiluminescence immunoassay.. Circulating cTnT levels were higher in women with DM1, DM2 and GDM as compared to controls, whereas NT-proBNP and GDF-15 levels were only increased in women with DM1. Glucose dysregulation, assessed by third trimester HbA1c levels, positively correlated with all three CVD biomarker levels, whereas pregestational body mass index correlated negatively with GDF-15.. Our results support the presence of myocardial affection in women with diabetic disorders during pregnancy. Although pregestational DM1 in this study was associated with the most adverse CVD biomarker profile, women with GDM displayed an adverse cTnT profile similar to what we found in women with pregestational DM2. This supports that women with GDM should be offered long-term intensified cardiovascular follow-up and lifestyle advice following delivery, similarly to the well-established CV follow-up of women with pregestational DM.

Topics: Biomarkers; Blood Glucose; Cardiovascular Diseases; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetes, Gestational; Female; Growth Differentiation Factor 15; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Pregnancy; Troponin T

This study performed a prediction and risk factor analysis of diuretic resistance (DR) in patients with decompensated heart failure during hospitalization.. The data of patients with decompensated heart failure treated in 2010-2018 with DR (n = 3,383) or without DR (n = 15,444) were retrospectively collected from Chinese PLA General Hospital medical records. Statistical analysis of baseline was performed on two groups of people, and the risk factor of DR was analyzed through logic regression. Six machine learning models were built accordingly, and the adjustment of model super parameters was performed by using Bayesian optimization method. Finally, the optimal algorithm was selected according to prediction efficiency.. The DR risk prediction model based on a gradient boosting decision tree created here identified its important risk factors. The model made very accurate predictions using simple indicators and simultaneously calculated cutoff values to help doctors predict the occurrence of DR.

Topics: Bayes Theorem; Diabetes Mellitus, Type 2; Diuretics; Factor Analysis, Statistical; Heart Failure; Hospitalization; Humans; Middle Aged; Natriuretic Peptide, Brain; Retrospective Studies; Risk Factors; Serum Albumin

Type 2 diabetes mellitus (T2DM) is a well-established risk factor for cardiovascular diseases. We aimed to identify the biological variation of ten cardiovascular biochemical markers in T2DM patients to aid in their interpretation.. Blood samples for evaluating ten biomarkers were collected biweekly from 23 T2DM patients (10 men, 13 women) for three months. The analytical variability and variations of within-subject (CV. The levels of total cholesterol (CHOL), apolipoprotein A (apoA), homocysteine (HCY), high-sensitivity troponin T (hsTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) differed between males and females (P < 0.05). The CV. The cardiovascular biochemical markers in T2DM patients showed higher CV

Topics: Apolipoproteins A; Biomarkers; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Female; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Troponin T

Recent studies have demonstrated that hyperglycemia is a major risk factor for the development and exacerbation of cardiovascular disease (CVD). However, the molecular mechanisms involved in diabetic cardiomyopathy (DCM) have not been fully elucidated. In this study, we focused on the underlying mechanism of DCM. Leptin receptor-deficient db/db mice were used to model a type 2 diabetes mellitus (T2DM) model in our study. WT mice and db/db mice received 4-phenylbutyric acid (4-PBA) (25 mg/kg/day) and saline by intraperitoneal injection every other day for 4 weeks. WT and db/db mice were given tail vein injections of 100 μL of rAAV9-Sh-MAPK10 and rAAV9-Sh-GFP at the age of 6-8 weeks. Echocardiography was performed to measure cardiac function, histological examinations were used to evaluate ventricular hypertrophy and fibrosis. Quantitative RT-qPCR was used to assess the mRNA expression of Jun N-terminal kinase 3 (JNK3, MAPK10), atrial natriuretic factor (ANF), brain natriuretic peptide (BNP), and collagen I and III. Immunoblotting was performed to measure the levels of cardiac hypertrophy-related proteins, fibrosis-related proteins, endoplasmic reticulum stress (ERS)-related proteins and apoptosis-related proteins. TUNEL staining was performed to examine cardiomyocyte apoptosis. In contrast to 12-week-old db/db mice, 16-week-old db/db mice showed the most severe myocardial dysfunction. The DCM induced by hyperglycemia was largely alleviated by 4-PBA (25 mg/kg/day, intraperitoneal injection). Similarly, tail vein injection of rAAV9-Sh-MAPK10 reversed the phenotype of the heart in db/db mice including cardiac hypertrophy and apoptosis in db/db mice. The mechanistic findings suggested that hyperglycemia initiated the ERS response through the negative regulation of sirtuin 1 (SIRT1), leading to the occurrence of myocardial dysfunction, and specific knockdown of MAPK10 in the heart directly reversed myocardial dysfunction induced by hyperglycemia. We demonstrated that hyperglycemia promotes DCM in db/db mice through the ERS-MAPK10 signaling pathway in diabetic mice.

Topics: Animals; Atrial Natriuretic Factor; Cardiomegaly; Cardiomyopathies; Collagen; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Endoplasmic Reticulum Stress; Fibrosis; Hyperglycemia; JNK Mitogen-Activated Protein Kinases; Mice; Mitogen-Activated Protein Kinase 10; Natriuretic Peptide, Brain; Receptors, Leptin; RNA, Messenger; Signal Transduction; Sirtuin 1

Aim      To study the incidence and clinical and pathophysiological features of diastolic dysfunction (DD) and chronic heart failure with preserved ejection fraction (HFpEF) in patients with resistant arterial hypertension (RAH) associated with type 2 diabetes mellitus (DM).Material and methods  A cross-sectional study that included 36 patients with RAH associated with type 2 DM (mean age, 61.4±6.4 years; 14 men) was performed. Measurement of office and 24-h blood pressure (BP), standard echocardiography with assessment of diastolic function (DF) and ventricular-arterial coupling, doppler ultrasound imaging of renal blood flow, and laboratory tests (blood glucose, glycated hemoglobin, blood creatinine, tumor necrosis factor α (TNF-α), brain natriuretic peptide (BNP), type 2 and type 9 matrix metalloproteinases (MMP-2 and MMP-9), tissue inhibitor of MMP 1 (TIMP-1), 24-h urine protein test, and 24-h urine volume test were performed for all patients. HFpEF was diagnosed according to criteria of the American Society of Echocardiography and the European Society of Cardiology 2019, and the Russian Clinical Guidelines on Diagnosis and Treatment of CHF 2017 and 2020.Results All patients had DD. Incidence of HFpEF detection according to the Russian Guidelines 2017 was 100%; according to the Russian Guidelines 2020, that included a required increase in BNP, and according to the criteria of the European Guidelines 2019, this incidence was 89 %. In 55.6 % of patients, DD corresponded to grade 2 (pseudonormal type). According to the correlation analysis, the DF impairment was associated with increases in pulse BP, myocardial mass, arterial and left ventricular elastance (arterial wall and left ventricular elasticity), basal glycemia and DM duration, MMP-2 level, proteinuria, blood creatinine, renal vascular resistance, and also with decreases in 24-h urine volume, MMP-9, TIMP-1, and TIMP-1/MMP-2. Significance of the relations of mean E / e' ratio with nighttime pulse BP, MMP-9, and 24-h urine volume were confirmed by results of multiple linear regression analysis. Increased myocardial and vascular wall stiffness, concentrations of MMP-2 and TNF-α and reduced 24-h urine volume were associated with progressive impairment of DF.Conclusion      The combination of RAH and DM-2 is characterized by an extremely high incidence of DD that determines a great prevalence of HFpEF. The development and progression of DD in such patients are closely related with a complex of metabol

Topics: Aged; Creatinine; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Heart Failure; Humans; Hypertension; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Middle Aged; Natriuretic Peptide, Brain; Stroke Volume; Tissue Inhibitor of Metalloproteinase-1; Tumor Necrosis Factor-alpha

Patients with type 2 diabetes (T2DM) present an increased risk of cardiovascular (CV) disease and excess CV-related mortality. Beyond the established role of brain natriuretic peptide (BNP) and cardiac troponins (cTn), other non-cardiac-specific biomarkers are emerging as predictors of CV outcomes in T2DM.. Serum levels of soluble suppression of tumorigenesis 2 (sST2), high-sensitivity (hs)-cTnI, and N-terminal (NT)-proBNP were assessed in 568 patients with T2DM and 115 healthy controls (CTR). Their association with all-cause mortality and the development of diabetic complications was tested in T2DM patients over a median follow-up of 16.8 years using Cox models and logistic regressions.. sST2 followed an increasing trend from CTR to uncomplicated T2DM patients (T2DM-NC) to patients with at least one complication (T2DM-C), while hs-cTnI was significantly higher in T2DM-C compared to CTR but not to T2DM-NC. A graded association was found between sST2 (HR 2.76 [95% CI 1.20-6.33] for ≥ 32.0 ng/mL and 2.00 [1.02-3.94] for 16.5-32.0 ng/mL compared to < 16.5 ng/mL, C-statistic = 0.729), NT-proBNP (HR 2.04 [1.90-4.55] for ≥ 337 ng/L and 1.48 [1.05-2.10] for 89-337 ng/L compared to < 89 ng/L, C-statistic = 0.741), and 15-year mortality in T2DM, whereas increased mortality was observed in patients with hs-cTnI ≥ 7.8 ng/L (HR 1.63 [1.01-2.62]). A 'cardiac score' based on the combination of sST2, hs-cTnI, and NT-proBNP was significantly associated with all-cause mortality (HR 1.35 [1.19-1.53], C-statistic = 0.739) and development of CV events.. sST2, hs-cTnI, and NT-proBNP are associated with 15-year mortality and onset of CV events in T2DM. The long-term prognostic value of sST2 and its ability to track variables related to insulin resistance and associated metabolic disorders support its implementation into routine clinical practice.

Topics: Cardiovascular Diseases; Diabetes Mellitus, Type 2; Humans; Interleukin-1 Receptor-Like 1 Protein; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Retrospective Studies; Troponin I; Troponin T

N-terminal pro-B-type natriuretic peptide (NT-proBNP) is suggested to be altered in patients with systolic heart failure or acute coronary syndrome. We explored the relationship between left ventricular ejection fraction (LVEF) and levels of NT-proBNP in patients with unstable angina and type 2 diabetes mellitus and preserved LVEF.Patients with unstable angina were divided into normal glucose tolerance (controls) and type 2 diabetes mellitus groups. The plasma NT-proBNP concentration was measured in these patients within 30 minute of admission for a comparative study. The severity of coronary arterial lesions was evaluated using Syntax scores. Results: NT-proBNP levels were not significantly different in patients with unstable angina and type 2 diabetes mellitus (median [quartiles]: 167.0 [66.1, 623.3] pg/mL) from those of controls (116.0 [69.8, 233.0], P = 0.278). Subsequent analyses indicated that ln (NT-proBNP) was positively associated with the following parameters: left ventricular end-diastolic diameter (r = 0.495, P = 0.019), left ventricular end-systolic diameter (r = 0.648, P = 0.001), and Syntax score (r = 0.567, P = 0.006); ln (NT-proBNP) was negatively associated with LVEF (r = -0.652, P = 0.001) in patients with unstable angina and type 2 diabetes mellitus. In multiple linear regression analysis, ln (NT-proBNP) levels were significantly independently correlated with the LVEF and Syntax score. However, no correlation was observed between ln (NT-proBNP) and each parameter in patients with unstable angina and normal glucose tolerance (controls).The NT-proBNP level is independently correlated with the LVEF in patients with unstable angina and type 2 diabetes mellitus and preserved LVEF.

Topics: Angina, Unstable; Biomarkers; Diabetes Mellitus, Type 2; Glucose; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Stroke Volume; Ventricular Function, Left

This study was to investigate the correlation between glycated haemoglobin (HbA1c) level, cardiac function, and prognosis in patients with diabetes mellitus combined with myocardial infarction.. Ninety-three patients with type 2 diabetes mellitus combined with acute myocardial infarction who were hospitalized and treated in our hospital from January 2021 to June 2021 were recruited for prospective analysis and equally divided into group A (HbA1c < 6.5%), group B (6.5% ≤ HbA1c ≤ 8.5%), and group C (HbA1c > 8.5%) using the random number table method, with 31 patients in each group. General data of patients were collected on admission and blood glucose and cardiac function indexes were measured; the incidence of myocardial infarction and death during the follow-up period was recorded at 6 months after discharge.. There was a significant difference in blood glucose (FBG) and HbA1c levels at fasting between the three groups (. HbA1c level in patients with diabetes mellitus combined with myocardial infarction is closely related to the degree of cardiac function damage. Glycated haemoglobin levels are associated with the development of cardiac insufficiency in patients with acute myocardial infarction; glycated haemoglobin is also an independent predictor of major adverse cardiovascular events. Reasonable and effective blood glucose control is of great significance to the prognosis of patients.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Myocardial Infarction; Natriuretic Peptide, Brain; Prognosis; Stroke Volume; Uric Acid; Ventricular Function, Left

Natriuretic peptide (NP) concentrations are increased in cardiovascular diseases (CVDs) but are associated with a lower diabetes risk. We investigated associations of N-terminal pro-B-type NP (NT-proBNP) and midregional proatrial NP (MR-proANP) with incident type 2 diabetes stratified by the presence of CVD.. Based on the Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE) Consortium, we included 45,477 participants with NT-proBNP measurements (1,707 developed type 2 diabetes over 6.5 years of median follow-up; among these, 209 had CVD at baseline) and 11,537 participants with MR-proANP measurements (857 developed type 2 diabetes over 13.8 years of median follow-up; among these, 106 had CVD at baseline). The associations were estimated using multivariable Cox regression models.. Both NPs were inversely associated with incident type 2 diabetes (hazard ratios [95% CI] per 1-SD increase of log NP: 0.84 [0.79; 0.89] for NT-proBNP and 0.77 [0.71; 0.83] for MR-proANP). The inverse association between NT-proBNP and type 2 diabetes was significant in individuals without CVD but not in individuals with CVD (0.81 [0.76; 0.86] vs. 1.04 [0.90; 1.19];. NT-proBNP and MR-proANP are inversely associated with incident type 2 diabetes. However, the inverse association of NT-proBNP seems to be modified by the presence of CVD. Further investigations are warranted to confirm our findings and to investigate the underlying mechanisms.

Topics: Atrial Natriuretic Factor; Biomarkers; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Heart Disease Risk Factors; Humans; Natriuretic Peptide, Brain; Natriuretic Peptides; Peptide Fragments; Risk Assessment; Risk Factors

Use of galectin-3 for assessing cardiac function in prediabetes and type 2 diabetes mellitus (T2DM) needs to be established. Within the Gutenberg Health Study cohort (N = 15,010, 35-74 years) patient characteristics were investigated regarding galectin-3 levels. Prognostic value of galectin-3 compared to NT-proBNP concerning cardiac function and mortality was assessed in individuals with euglycaemia, prediabetes and T2DM in 5 years follow-up. Higher galectin-3 levels related to older age, female sex and higher prevalence for prediabetes, T2DM, cardiovascular risk factors and comorbidities. Galectin-3 cross-sectionally was related to impaired systolic (β - 0.36, 95% CI - 0.63/- 0.09; P = 0.008) and diastolic function (β 0.014, 95% CI 0.001/0.03; P = 0.031) in T2DM and reduced systolic function in prediabetes (β - 0.34, 95% CI - 0.53/- 0.15; P = 0.00045). Galectin-3 prospectively related to systolic (β - 0.656, 95% CI - 1.07/- 0.24; P = 0.0021) and diastolic dysfunction (β 0.0179, 95% CI 0.0001/0.036; P = 0.049), cardiovascular (hazard ratio per standard deviation of galectin-3 (HR

Topics: Adult; Aged; Biomarkers; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Diastole; Female; Follow-Up Studies; Galectin 3; Heart; Heart Disease Risk Factors; Heart Function Tests; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prediabetic State; Systole

Background Sodium-glucose cotransporter 2 inhibitors improve cardiovascular outcomes in patients with diabetes with and without heart failure (HF). However, their influence on sympathetic nerve activity (SNA) remains unclear. The purpose of this study was to evaluate the effect of sodium-glucose cotransporter 2 inhibitors on SNA and compare the responses of SNA to sodium-glucose cotransporter 2 inhibitors in patients with type 2 diabetes with and without HF. Methods and Results Eighteen patients with type 2 diabetes, 10 with HF (65.4±3.68 years) and 8 without HF (63.3±3.62 years), were included. Muscle SNA (MSNA), heart rate, and blood pressure were recorded before and 12 weeks after administration of dapagliflozin (5 mg/day). Sympathetic and cardiovagal baroreflex sensitivity were simultaneously calculated. Brain natriuretic peptide level increased significantly at baseline in patients with HF than those without HF, while MSNA, blood pressure, and hemoglobin A1c did not differ between the 2 groups. Fasting blood glucose and homeostatic model assessment of insulin resistance did not change in either group after administering dapagliflozin. MSNA decreased significantly in both groups. However, the reduction in MSNA was significantly higher in patients with HF than patients with non-HF (-20.2±3.46 versus -9.38±3.65 bursts/100 heartbeats;

Topics: Benzhydryl Compounds; Blood Glucose; Diabetes Mellitus, Type 2; Glucosides; Heart Failure; Humans; Muscles; Natriuretic Peptide, Brain; Sodium; Sodium-Glucose Transporter 2 Inhibitors; Sympathetic Nervous System

Recently, the European Society of Cardiology (ESC) and European Association for the Society of Diabetes (EASD) introduced a new cardiovascular disease (CVD) risk stratification model to aid further treatment decisions in individuals with diabetes. Our study aimed to investigate the prognostic performance of the ESC/EASD risk model in comparison to the Systematic COronary Risk Evaluation (SCORE) risk model and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in an unselected cohort of type 2 diabetes mellitus (T2DM).. A total of 1690 T2DM patients with a 10-year follow up for fatal CVD and all-cause death and a 5-year follow up for CVD and all-cause hospitalizations were analyzed. According to ESC/EASD risk criteria 25 (1.5%) patients were classified as moderate, 252 (14.9%) high, 1125 (66.6%) very high risk and 288 (17.0%) were not classifiable. Both NT-proBNP and SCORE risk model were associated with 10-year CVD and all-cause death and 5-year CVD and all-cause hospitalizations while the ESC/EASD model was only associated with 10-year all-cause death and 5-year all-cause hospitalizations. NT-proBNP and SCORE showed significantly higher C-indices than the ESC/EASD risk model for CVD death [0.80 vs. 0.53, p < 0.001; 0.64 vs. 0.53, p = 0.001] and all-cause death [0.73, 0.66 vs. 0.52, p < 0.001 for both]. The performance of SCORE improved in a subgroup without CVD aged 40-64 years compared to the unselected cohort, while NT-proBNP performance was robust across all groups.. The new introduced ESC/EASD risk stratification model performed limited compared to SCORE and single NT-proBNP assessment for predicting 10-year CVD and all-cause fatal events in individuals with T2DM.

Topics: Age Factors; Aged; Austria; Biomarkers; Cardiovascular Diseases; Cause of Death; Comorbidity; Decision Support Techniques; Diabetes Mellitus, Type 2; Female; Heart Disease Risk Factors; Hospitalization; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Prospective Studies; Registries; Risk Assessment; Time Factors

Diagnostic tests including echocardiography, albuminuria, electrocardiogram (ECG), high-sensitivity troponin I (hs-TnI), and N-terminal prohormone brain natriuretic peptide (NT-proBNP) have been suggested as cardiovascular (CV) risk predictors in type 2 diabetes. We studied the separate and combined prognostic yield of these risk markers.. In all, 1030 patients with type 2 diabetes were recruited from specialized clinics in this prospective cohort study. Full echocardiographic evaluation was feasible in 886 patients in sinus rhythm with adequate image quality. ECG was performed in 998 patients. Albuminuria was measured in 1009 and NT-proBNP/hs-TnI in 933 patients. The end point was a composite of CV events.. The median follow-up was 4.7 years (interquartile range: 4.0-5.3), and 174 patients experienced a CV disease event. All considered markers, except hs-TnI, were significantly (P < .001) associated with the outcome: abnormal echocardiogram (hazard ratio 2.40 [1.70-3.39]), albuminuria 2.01 (1.47-2.76), abnormal ECG (2.27 [1.66-3.08]), high NT-proBNP (>150 pg/mL) 3.05 (2.11-4.40), and hs-TnI 1.12 (0.79-1.59). After adjusting for clinical variables, all remained significantly associated with the end point. However, after adjusting for each other, only NT-proBNP >150 pg/mL remained significantly associated with the end point (2.07 [1.28-3.34], P < .001). Measured by C-statistics, model performance was highest with log. This study identified NT-proBNP over echocardiography, ECG, and albuminuria in risk prediction in patients with type 2 diabetes. The diagnostic yield in considering more than one risk marker was limited in this population.. 背景: 超声心动图、蛋白尿、心电图(ECG)、高敏肌钙蛋白I(hs-TnI)和N末端前激素脑钠素(NT-proBNP)等诊断试验被认为能够预测2型糖尿病心血管(CV)的危险因素。我们研究了这些风险标记物的单独和联合预测效果。 方法: 在这项前瞻性队列研究中, 从专科诊所共招募1030名2型糖尿病患者。886例窦性心律且图像质量良好的患者进行了超声心动图的全面评估。对998例患者进行心电图检查。1009例患者检测蛋白尿, 933例患者检测NT-proBNP/hs-TnI。终点是CV事件的组合。 结果: 中位随访时间为4.7年(四分位数范围:4.0-5.3), 174名患者经历了心血管疾病事件。除hs-TnI外, 所有考虑的标志物:超声心动图异常(危险比2.40[1.70-3.39])、蛋白尿2.01(1.47-2.76)、心电图异常(2.27[1.66-3.08])、高NT-proBNP(>150pg/mL)3.05(2.11-4.40)和hs-TnI 1.12(0.79-1.59) 均与预后显著相关(P<0.001)。在调整了临床变量后, 所有这些变量仍然与终点显著相关。然而, 在变量间调整后, 只有NT-proBNP>150pg/mL与终点显著相关(2.07[1.28-3.34], P<0.001)。通过C-统计量测量, log

Topics: Aged; Albuminuria; Biomarkers; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Electrocardiography; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Prospective Studies; Risk Factors; Ultrasonography; Urinalysis

Altered circulating levels and genetic variation of B-type natriuretic peptide (BNP), has been associated with lower bone mineral density (BMD) values and incidence of osteoporosis in peritoneal dialysis patients, renal transplant recipients, and postmenopausal women. The potential relationship of circulating BNP with osteoporosis in patients with type 2 diabetes mellitus (T2DM), however, has not yet been studied.. Circulating BNP levels were measured in 314 patients with T2DM, and participants were divided into normal BMD group (n = 73), osteopenia group (n = 120), and osteoporosis group (n = 121). The association of circulating BNP with diabetic osteoporosis and other parameters was analyzed.. Circulating BNP was significantly higher in diabetic osteoporosis subjects than normal and osteopenia groups (P < 0.01 or P < 0.05). Circulating BNP levels correlated significantly and positively with neutrophil to lymphocyte ratio, systolic blood pressure, urinary albumin-to-creatinine ratio, and prevalence of hypertension, peripheral arterial disease, diabetic retinopathy, peripheral neuropathy, and nephropathy, and negatively with triglyceride, fasting blood glucose, lymphocyte count, hemoglobin, estimated glomerular filtration rate, bilirubin, osteoporosis self-assessment tool for Asians, BMD at different skeletal sites and corresponding T scores (P < 0.01 or P < 0.05). After multivariate adjustment, circulating BNP remained independently significantly associated with the presence of osteoporosis (odds ratio, 2.710; 95% confidence interval, 1.690-4.344; P < 0.01). BMD at the femoral neck and total hip and corresponding T scores were progressively decreased, whereas the prevalence of osteoporosis was progressively increased with increasing BNP quartiles (P for trend< 0.01). Moreover, receiver-operating characteristic analysis revealed that the optimal cutoff point of circulating BNP to indicate diabetic osteoporosis was 16.35 pg/ml.. Circulating BNP level may be associated with the development of osteoporosis, and may be a potential biomarker for diabetic osteoporosis.

Topics: Asian People; Bone Density; China; Diabetes Mellitus, Type 2; Female; Humans; Natriuretic Peptide, Brain; Osteoporosis

Numerous biomarkers of diabetic kidney disease (DKD) are associated with renal prognosis but head-to-head comparisons are lacking. This study aimed to examine the association of soluble tumor necrosis factor receptor type 1 (sTNFR1), fibroblast growth factor 21 (FGF-21), endocan, N-terminal pro-brain natriuretic peptide (NT-pro-BNP), and renal outcomes of patients with or without clinical signs of DKD.. Higher sTNFR1 and FGF-21, rather than endocan and NT-pro-BNP, levels were associated with renal outcomes but the significance was lost after adjusting for confounders. However, sTNFR1 levels ≥ 9.79 pg/dL or FGF-21 levels ≥ 1.40 pg/dL were associated with renal outcomes after adjusting for the confounders (hazard ration [HR] 2.76, 95% confidence interval [CI] 1.36-5.60, p = 0.005 for sTNFR1 level; HR 1.95, 95% CI 1.03-3.69, p = 0.03 for FGF-21 level). The combination of both levels exhibited even better association with renal outcomes than did either one alone (adjusted HR 4.45, 95% CI 1.86-10.65, p = 0.001). The results were consistent among patients with preserved renal function and normoalbuminuria.. Both sTNFR1 and FGF-21 levels were associated with renal outcomes of in patients with type 2 diabetes, and the combination of the abovementioned markers exhibits better predictability.

Topics: Biomarkers; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Female; Fibroblast Growth Factors; Humans; Kidney Function Tests; Male; Middle Aged; Natriuretic Peptide, Brain; Neoplasm Proteins; Outcome Assessment, Health Care; Peptide Fragments; Predictive Value of Tests; Prognosis; Prospective Studies; Proteoglycans; Receptors, Tumor Necrosis Factor, Type I

We aimed to evaluate the trajectory of two surrogates of fluid overload -antigen carbohydrate 125 (CA125) and amino-terminal pro-brain natriuretic peptide (NT-proBNP)- after the addition of oral empagliflozin to usual care in a cohort of patients with chronic heart failure (CHF) and type 2 diabetes (T2D).. From October 2015 to February 2019, 60 ambulatory patients with CHF and T2D were retrospectively included. The primary endpoint was to assess the longitudinal trajectory of plasma levels of CA125 and NT-proBNP after empagliflozin initiation. Changes in quantitative variables were evaluated using linear mixed regression. Median CA125 and NT-proBNP at baseline were 17 (11-75) U/mL and 1662 (647-4230) pg/mL, respectively. A total of 510 outpatient visits were recorded [median (interquartile range) of visits per patient: 6 (4-11)] during a median of 1.78 years. We found a significant and steady decrease in the log of CA125 after empagliflozin initiation (p < 0.001). Conversely, the log of NT-proBNP predicted trajectory did not significantly change (p = 0.425).. In this cohort of patients with CHF and T2D, empagliflozin initiation was associated with a significant decrease in CA125 levels without modifying the trajectory of NT-proBNP. Considering that CA125 has emerged as a surrogate marker of tissue congestion, we hypothesize that empagliflozin might predominantly promote extravascular decongestion.

Topics: Benzhydryl Compounds; Biomarkers; Diabetes Mellitus, Type 2; Glucosides; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Retrospective Studies

Sodium-glucose cotransporter 2 inhibitor (SGLT2i) reduces the risk of the composite renal endpoint and weakens the progressive decline in renal function in patients with chronic heart failure (HF). However, a detailed mechanism of SGLT2i on renal function and outcome remains uninvestigated.. We prospectively included 40 type 2 diabetic mellitus (T2DM) patients (median 68 years old, 29 male) who were hospitalized for decompensated HF and received SGLT2i during the index hospitalization. Of them, 24 patients had increases in estimated glomerular filtration rate (eGFR) at 12-month follow-up and 16 had decreases in eGFR. We investigated the baseline factors associating with the improvement in renal function.. Lower plasma B-type natriuretic peptide (BNP) level and the use of renin-angiotensin system inhibitor (RASI) were independently associated with increases in eGFR during the follow-up period (p < 0.05 for both). Patients with both low plasma BNP levels and uses of RASI achieved significant increases in eGFR irrespective of the baseline HbA1c levels.. Lower plasma BNP level and the use of RASI at baseline were the key factors contributing to the renoprotective effects of SGLT2i among patients with decompensated HF and T2DM.

Topics: Aged; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Biomarkers; Diabetes Mellitus, Type 2; Disease Progression; Female; Glomerular Filtration Rate; Heart Failure; Humans; Kidney; Male; Middle Aged; Natriuretic Peptide, Brain; Recovery of Function; Registries; Renal Insufficiency, Chronic; Retrospective Studies; Risk Factors; Sodium-Glucose Transporter 2 Inhibitors; Time Factors; Treatment Outcome

Based on the complex pathophysiology of type 2 diabetes and atherosclerosis we hypothesized a dynamic change in prognostic value of cardiovascular biomarkers over time.. In this prospective study 746 patients with type 2 diabetes mellitus, being followed up for 60 months were analysed. The primary endpoint was defined as unplanned hospitalization for cardiovascular disease or death. Beside others, especially the prognostic performance of the biomarkers of interest (GDF-15, NT-proBNP, hs-TnT) was evaluated in relation to quartiles of diabetes duration.. In patients having a diabetes duration below 7 years lnGDF-15 (HR 2.84; p < 0.01) and lnhs-TnT (HR 2.96; p < 0.01) were significant predictors of the primary endpoint. LnAge (HR 40.01; p < 0.01) and lnNT-proBNP (HR 1.56; p = 0.03) were significant predictors in patients with a diabetes duration between 7 and 12 years. In the third quartile (diabetes duration 12-22 years) lnurinary albumin to creatinine ratio (HR 1.25; p = 0.005) and lnNT-proBNP (HR 2.13, p < 0.001) predicted the endpoint. In patients with a diabetes duration above 22 years, lnAge (HR 75.35; p = 0.001) and lnNT-proBNP (HR 2.0; p < 0.01) were the only significant predictors of the endpoint.. Prognostic power of cardiovascular biomarkers changes dynamically in relation to duration of type 2 diabetes mellitus. In patients with shorter duration of the disease markers of subclinical cardiovascular dysfunction and inflammation perform better than markers of systemic advanced organ dysfunction and cardiovascular disease.

Topics: Biomarkers; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Growth Differentiation Factor 15; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Prospective Studies; Time Factors; Troponin T

Natriuretic peptides are cardiac-derived hormones that enhance insulin sensitivity and reduce fat accumulation. Low natriuretic peptide levels are associated with increased risk of type 2 diabetes mellitus (DM2); a condition with variable prevalence across racial/ethnic groups. Few studies have examined whether circulating natriuretic peptide levels and their response to preventive interventions for DM2 differ by race/ethnicity. The Diabetes Prevention Program (DPP) is a clinical trial (July 31, 1996- July 31, 2001) that randomized participants to preventive interventions for DM2. Using stored serum samples, we examined N-terminus pro-B-type natriuretic peptide (NT-proBNP) levels in 3,220 individuals (56% white; 19% African-American; 15% Hispanic; 5% American-Indian; 5% Asian). The influence of race/ethnicity on NT-proBNP concentrations at baseline and after two years of treatment with placebo, lifestyle, or metformin was examined with multivariable-adjusted regression. At baseline, NT-proBNP differed significantly by race (P < .001), with the lowest values in African-American individuals. Hispanic individuals also had lower baseline NT-proBNP levels compared with whites (P< .001), while NT-proBNP levels were similar between white, American-Indian, and Asian individuals. At two years of follow-up, NT-proBNP levels decreased in African-Americans in each of the DPP study arms, whereas they were stable or increased in the other racial/ethnic groups. In the DPP, African-American individuals had lower circulating NT-proBNP levels compared with individuals in other racial/ethnic groups at baseline and after two years of preventive interventions. Further studies should examine the cardio-metabolic implications of lower natriuretic peptide levels in African-Americans. Trial Registration: ClinicalTrials.gov NCT00004992.

Topics: Adult; Diabetes Mellitus, Type 2; Ethnicity; Female; Humans; Life Style; Male; Metformin; Middle Aged; Natriuretic Peptide, Brain; Natriuretic Peptides; Peptide Fragments; Racial Groups; Randomized Controlled Trials as Topic

The role of NT-proBNP and hs-cTnT levels in predicting heart failure (HF) and cardiovascular disease (CVD) events in persons with prediabetes (pre-DM) and diabetes mellitus (DM) is not well-established. We examined the individual and combined relations of N-terminal natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) levels among asymptomatic adults with pre-DM and DM with the development of incident HF and CVD events. 5,584 participants with biomarker measures aged 45 to 84 years were included from the Multi-Ethnic Study of Atherosclerosis, of which 4,090 were normoglycemic, 799 had pre-DM, and 695 had DM at baseline and were followed for 12.4 ± 3.8 years. In those with DM, HF incidence rates per 1,000 person-years ranged from 3.2 to 39.4 across quartiles of NT-proBNP and 0.6 to 18.2 for hs-cTnT, respectively. Corresponding values for CVD incidence per 1,000 person-years ranged from 13.7 to 39.4 for NT-proBNP and 13.2 to 35.4 for hs-cTnT. Multivariate adjusted HRs were highest when both NT-proBNP and hs-cTnT were above versus below the median in those with pre-DM/DM (16.7 for incident HF and 2.1 for CVD events, both p <0.01). In conclusion, the combination of both biomarkers to traditional risk factors in participants who were normoglycemic or with pre-DM or DM improved risk prediction for both incident HF and total CVD events in an ethnically diverse population.

Topics: Aged; Aged, 80 and over; Angina Pectoris; Blood Glucose; Cardiovascular Diseases; Coronary Disease; Diabetes Mellitus, Type 2; Female; Heart Failure; Humans; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Prediabetic State; Risk Assessment; Stroke; Troponin T; United States

Objective Investigate the role of biomarkers in the prognosis of the clinical course of the disease in patients with chronic heart failure (CHF) of different NYHA functional classes (FC).Material and Methods The study included 132 patients with CHF: Group 1 was composed of 70 patients with NYHA FC II CHF, and Group 2 included 62 patients with FC III-IV CHF. The patients underwent clinical, instrumental, functional, and laboratory measurements, which included serum concentrations of NT-proBNP, ST-2, galectin-3, and C-reactive protein. Patients were examined at baseline and at 3, 6, and 12 mos of follow-up. The following cardiac complications were used as endpoints: urgent hospitalization due to decompensated CHF, heart transplantation, cardiovascular death. Endpoints were registered during the 12-mo follow-up period.Results Endpoints were recorded for 58 patients (44%) of the total sample of patients with CHF: 38 patients were urgently hospitalized, 10 patients underwent heart transplantation, 10 patients died. Cardiac complications were recorded at a higher rate in patients with FC III-IV CHF (63% vs. 27% of patients with FC II; p<0.001). In FC II CHF patients, the incidence of cardiac complications was significantly correlated with NT-proBNP blood concentrations (Rpb=0.53; p=0.023), left ventricular end-diastolic volume (LVEDV) (Rpb=0.50; p=0.044), and mitral regurgitation (Rpb=0.53; p=0.038). Cardiac complications in patients with FC III-IV CHF were associated with ST-2 (Rpb=0.52; p=0.004) and galectin-3 (Rpb=0.46; p=0.009) blood concentrations, and with systolic pulmonary artery pressure (PAP) (Rpb=0.41; p=0.014). Unlike other laboratory measurements, galectin-3 concentrations were significantly correlated with type 2 diabetes mellitus (DM2) (Rpb=0.40; p=0.003). In this study, correlation analysis and evidence of significant differences in the concentrations of biomarkers provided a rationale for identifying potential predictors of severe cardiac complications during medium- and long-term follow-up periods in patients with CHF of different severity: NT-proBNP concentrations in FC II patients; ST-2 and galectin-3 serum concentrations in FC III-IV patients; galectin-3 concentrations in patients with CHF and DM2.Conclusion NT-proBNP blood concentrations are associated with CHF severity and serious cardiac complications in patients with FC II CHF within the following 12 mos. The poor prognosis of FC III-IV CHF is associated with the concentration of the

Topics: Biomarkers; Chronic Disease; Diabetes Mellitus, Type 2; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis

Cardiovascular diseases (CVD) are the major causes of mortality in patients with type 2 diabetes mellitus (T2DM). There is paucity of information on prevalence of subclinical atherosclerosis and cardiac dysfunction in young adults with T2DM. This study aimed to assess the prevalence of subclinical atherosclerosis and cardiac dysfunction in young adults with T2DM, asymptomatic for CVD.. Sixty-two patients with T2DM, age between 30 and 50 years were evaluated for coronary artery calcium (CAC) score, carotid intima-media thickness (CIMT) and flow-mediated dilatation (FMD) at the brachial artery. All were subjected to 2D-color Doppler echocardiography, electrocardiography and testing for serum N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-sensitivity C-reactive protein (hsCRP). The results were compared with those in 60 age, sex and BMI-matched healthy controls.. Prevalence of a positive CAC score was comparable among subjects with and without T2DM (14.5% vs 11.7%). Patients with T2DM had a significantly higher CIMT (0.54 ± 0.15 vs 0.49 ± 0.10 mm, p = 0.01), left ventricular (LV) mass (170 ± 36 vs 147 ± 23 g, p < 0.001), heart rate (83 ± 13 vs 74 ± 11, p < 0.001) and QTc interval (402 ± 20 vs 382 ± 21 ms, p < 0.001) compared to controls. FMD was lower in patients with T2DM compared to controls (9.1 ± 4.4% vs 10.7 ± 3.9%, p = 0.04). There was a higher prevalence of LV hypertrophy (37% vs 7%, p < 0.001) and diastolic dysfunction (7% vs 0) in patients with T2DM compared to controls. None of the participants had systolic dysfunction. Hypertension (42 vs 7%, p < 0.001) and metabolic syndrome (76 vs 35%, p < 0.001) were more prevalent in the patient group. In the multivariate analysis, age was the lone predictor of CIMT and FMD; while T2DM and male gender were the independent predictors of LV mass.. Young adults with T2DM, asymptomatic for CVD had a higher prevalence of CVD risk factors, LV hypertrophy and diastolic dysfunction. A higher CIMT and LV mass, and a lower FMD were noted in patients with T2DM. CAC score was comparable between the groups and thus may not be a useful tool for assessment of subclinical atherosclerosis in this cohort, where CIMT and FMD may be more appropriate.

Topics: Adult; Age Factors; C-Reactive Protein; Carotid Intima-Media Thickness; Case-Control Studies; Coronary Artery Disease; Diabetes Mellitus, Type 2; Echocardiography; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prevalence; Risk Factors; Vascular Calcification

Fluid overload is common in patients with diabetes and chronic kidney disease (DM and CKD; DMCKD) and can lead to structural and functional cardiac abnormalities including left ventricular hypertrophy (LVH) and left ventricular diastolic dysfunction (LVDD). Fluid overload represents a crucial step in the pathophysiological pathways to chronic heart failure in patients with end-stage renal disease. We evaluated the impact of fluid overload on cardiac alterations in patients with diabetes and non-dialysis-dependent CKD stage 5 (DMCKD5-ND) without intrinsic heart disease.. Bioimpedance spectroscopy, echocardiography, and N-terminal prohormone of B-type natriuretic peptide (NT-proBNP) measurement were performed in 135 consecutive patients on the same day. Patients were divided into groups by tertiles of overhydration/extracellular water (OH/ECW) per bioimpedance spectroscopy.. Fluid balance markers including OH/ECW and NT-proBNP were significantly higher in the LVDD+LVH group. OH/ECW and its exacerbation were positively associated with the ratio between early mitral inflow and annular early diastolic velocities (E/e' ratio) and left ventricular mass index (LVMI). The prevalence of LVH progressively increased across increasing tertiles of OH/ECW. In multiple regression analyses, OH/ECW as a continuous and categorical variable was independently associated with the E/e' ratio and LVMI after adjustment for multiple confounding factors.. Fluid overload was independently associated with LVDD and LVH in patients with DMCKD5-ND. Our study suggests that structural and functional cardiac abnormalities and volume status should be evaluated simultaneously in patients with early-stage DMCKD rather than only DMCKD5-ND, in addition to intensive blood pressure and glycemic control, regardless of evident cardiovascular disease.

Topics: Aged; Diabetes Mellitus, Type 2; Dielectric Spectroscopy; Echocardiography; Female; Fluid Therapy; Glomerular Filtration Rate; Humans; Hypertrophy, Left Ventricular; Kidney Failure, Chronic; Linear Models; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prevalence; Renal Dialysis; Severity of Illness Index; Ventricular Dysfunction, Left

This study is aimed at investigating natriuretic peptide B (. The microarray dataset GSE26887, containing 19 postischemic HF patients' peripheral blood samples (7 with T2DM and 12 without T2DM), was examined to detect the genes coexpressed with. In patients with T2DM, a total of 41 biological processes (BP), 20 cellular components (CC), 13 molecular functions (MF), and 41 pathways were identified. Furthermore, a total of 61 BPs, 16 CCs, 13 MFs, and 22 pathways in patients without T2DM were identified. In both groups of patients, 17 BPs, 10 CCs, 6 MFs, and 13 pathways were enriched. We also identified 173 intersectional coexpression genes (63 positively, 106 negatively, and 4 differently coexpressed in patients with and without T2DM, respectively) in both types of patients, which were enriched in 16 BPs, 8 CCs, 3 MFs, and 8 KEGG pathways. Moreover, the PPI network (containing 237 edges and 170 nodes) with the top module significantly enriched in 4 BPs (tricarboxylic acid metabolic process, citrate metabolic process, tricarboxylic acid cycle, and aerobic respiration) and 3 pathways (citrate cycle, malaria parasite metabolic pathway, and AGE-RAGE signaling pathway in diabetic complications) was constructed.. Our findings may elucidate the functions and roles of the

Topics: Databases, Nucleic Acid; Diabetes Mellitus, Type 2; Gene Expression Regulation; Heart Failure; Humans; Myocardial Ischemia; Natriuretic Peptide, Brain

Circulating N-terminal pro B-type natriuretic peptide (NT-proBNP) is a classic diagnostic and prognostic marker for heart failure. However, it is inversely associated with diabetes risk. We aimed to investigate relationships of NT-proBNP with risk of diabetes-related complications in initially healthy individuals.. We performed a case-cohort study within the European Prospective Investigation Into Cancer and Nutrition (EPIC)-Potsdam cohort including a random subcohort (. In multivariable models, NT-proBNP was linearly inversely associated with incident type 2 diabetes with a hazard ratio (HR) (95% CI) per doubling in NT-proBNP of 0.91 (0.86, 0.98). The association was only observable in women (0.80 [0.72, 0.90]) compared with men (0.98 [0.91, 1.07]). Among people with incident diabetes, NT-proBNP was positively associated with diabetes complications: overall, 1.31 (1.13, 1.53); microvascular complications, 1.20 (1.01, 1.43); and macrovascular complications, 1.37 (1.03, 1.83).. Although higher NT-proBNP levels are associated with lower diabetes risk, NT-proBNP is a biomarker for vascular complications in people who develop diabetes independent of potential confounders. Thus, NT-proBNP might be informative to monitor risk for diabetes-related microvascular and macrovascular complications, which should be further explored in future prospective studies.

Topics: Adult; Aged; Biomarkers; Cardiovascular Diseases; Diabetes Complications; Diabetes Mellitus, Type 2; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Risk

Epidemiological and genetic studies have recorded the association between proinflammatory cytokines and the development of insulin resistance, diabetes, and cardiovascular disease. The role of interleukin 6 (IL-6), NH2-terminal portion pro-brain natriuretic peptide (NT-proBNP) and resistin in the pathogenesis of heart disease in type 2 diabetes mellitus (T2DM) is still a matter of controversy. The current study aimed to evaluate the role of these biomarkers in the development of left ventricular systolic dysfunction and the ability to use them as non-invasive test in the prediction of left ventricular hypertrophy and systolic dysfunction in T2DM.. 150 participants were included in this case-control study. Patients were divided into two subgroups according to echocardiographic findings: group 1a included 46 patients with type 2 diabetes mellitus and echocardiographic evidence of abnormal systolic function; group 1b included 54 patients with type 2 diabetes mellitus and with normal echocardiogenic study; and group 2 included 50 apparently healthy controls. Routine laboratory investigations such as complete blood count, liver and renal function tests, and lipid profile, serum IL-6, NT-proBNP, and resistin were measured in all participants. Conventional echocardiography was done with special concern on the assessment of left ventricular systolic function (ejection fraction).. There was a significant increase in the level of resistin, NT-proBNP and IL-6 in group 1a patients compared with group 1b and in healthy controls. Echocardiographic parameters showed a significant increase in left ventricular mass index, left ventricle posterior wall thickness, interventricular septum thickness, and left ventricle mass in group 1a compared with group 1b and the control group. The increased left ventricular mass index was associated with higher levels of IL-6, NT-proBNP and resistin.. Proinflammatory cytokines had a clear relation with left ventricular systolic dysfunction and hypertrophy and can be used as early non-invasive markers for detection of left ventricular remodeling and systolic dysfunction in patients with T2DM.

Topics: Case-Control Studies; Diabetes Mellitus, Type 2; Humans; Interleukin-6; Natriuretic Peptide, Brain; Resistin; Ventricular Dysfunction, Left

Topics: Adult; Aged; Aged, 80 and over; Anthropometry; Blood Pressure; China; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Female; Humans; Linear Models; Lymphocyte Count; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Predictive Value of Tests; Risk; ROC Curve

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are increasingly prescribed for the treatment of patients with type 2 diabetes to reduce the risk of cardiovascular events, including heart failure (HF). The mechanisms by which SGLT2 inhibitors reduce such risk are likely to be independent of diabetes status and improvement of glycemic control. In this commentary, based on recent mediation analyses of cardiovascular outcome trials with SGLT2 inhibitors, we discuss the prognostic role of a well-known HF-related biomarker, amino-terminal pro-B-type natriuretic peptide (NT-proBNP), in patients receiving SGLT2 inhibitors. Interestingly, the NT-proBNP concentration had a relatively small impact on the SGLT2 inhibitor-associated benefit on HF events, suggesting a limited value in measuring NT-proBNP concentrations to monitor effects on cardiovascular outcomes after initiation of SGLT2 inhibitor therapy. Instead, clinical factors, such as body weight and volume status, were prognostic for cardiovascular outcomes. As shown in some biomarker studies, short-term SGLT2 inhibitor treatment significantly improved volume and HF-related health status, despite the absence of a significant change in NT-proBNP concentration. Given the early and continuous risk reduction in HF events seen in the cardiovascular outcome trials with SGLT2 inhibitors, changes in these fundamental clinical parameters after initiation of SGLT2 inhibitor therapy, independent of NT-proBNP, could be more prognostic and could represent key determinants to identify responders or non-responders to SGLT2 inhibitors for cardiovascular outcomes. Thus, this commentary highlights the clinical importance of establishing how clinicians should monitor patients initiating SGLT2 inhibitor therapy to predict the expected cardiovascular benefit. Further detailed investigations and discussion to better understand this ''black box'' are urgently warranted.

Topics: Biomarkers; Blood Glucose; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Evidence-Based Medicine; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Risk Assessment; Risk Factors; Sodium-Glucose Transporter 2 Inhibitors; Time Factors; Treatment Outcome

Among all diabetes mellitus-associated cardiovascular diseases, morbidity of diabetic myocardium with ischemia reperfusion injury (D-IRI) is increasing year by year. We aimed to discover a therapeutic biomarker and investigate its mechanism in D-IRI. High-fat diet and streptozotocin-induced diabetes rats were operated with IRI or sham. Recombined lentiviral vector encoding Apelin was injected into D-IRI rat via tail vein. Cardiac function, infarct size, cellular death and oxidative stress were major outcome measures. Cardiomyocyte ischemia reperfusion injury was more serious in D-IRI rats than in non-diabetes ischemia reperfusion injury (ND-IRI) rats. The secretion of NTproBNP was increased in D-IRI compared with ND-IRI. Bcl-2 expression was decreased, and Bax and cleaved caspase-3 expression was increased in D-IRI rats compared with ND-IRI rats, which were reversed after treatment with Apelin. Apelin-upregulation improved cardiomyocyte ischemia reperfusion injury and decreased NT-proBNP levels in D-IRI rats. Apelin overexpression enhanced PI3K and eNOS levels while reduced those of p38-MAPK and iNOS in D-IRI rats. Apelin overexpression protected against D-IRI through inhibiting apoptosis and oxidative stress via PI3K and p38MAPK signaling pathways in D-IRI rats. These findings provide critical new insight into understanding of Apelin's cardio-protective effects, which may become a novel therapeutic target for the diabetic IRI patients.

Topics: Animals; Apelin; Apoptosis; bcl-2-Associated X Protein; Caspase 3; Cell Death; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Genetic Therapy; MAP Kinase Signaling System; Myocardial Reperfusion Injury; Myocardium; Myocytes, Cardiac; Natriuretic Peptide, Brain; Nitric Oxide Synthase Type II; Nitric Oxide Synthase Type III; Oxidative Stress; Peptide Fragments; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-bcl-2; Rats

Visceral fat area (VFA) is a good surrogate marker of obesity-related disorders, such as hypertension, dyslipidemia and glucose intolerance. Although estimating the VFA by X-ray computed tomography (CT) is the primary index for visceral obesity, it is expensive and requires invasive radiation exposure. Dual bioelectrical impedance analysis (BIA) is a simple and reliable method to estimate VFA; however, the clinical usefulness of dual BIA remains unclear in patients with type 2 diabetes (T2D).. We estimated the VFAs by dual BIA and CT in 98 patients with T2D and assessed anthropometric parameters, blood test results, and the presence of comorbid hypertension and dyslipidemia. We compared the correlation between the VFAs examined by dual BIA and CT. Furthermore, we performed the receiver operating characteristic (ROC) analyses for the VFAs to detect the presence of comorbid hypertension and/or dyslipidemia with T2D, which are major comorbidities of visceral obesity, and estimated the area under the curve (AUC).. The measurement error between the VFAs by dual BIA and CT was significantly higher among patients with brain natriuretic peptide (BNP) ≥ 100 pg/mL than those with BNP < 100 pg/mL (39.2% ± 31.1% vs. 24.1% ± 18.6%, P < 0.05). After excluding patients with BNP ≥ 100 pg/mL, the VFA by dual BIA significantly correlated with the VFA by CT (r = 0.917; P < 0.0001). The AUC in the ROC analysis for the VFA by dual BIA to detect the presence of comorbid hypertension and/or dyslipidemia with T2D was almost equivalent to that for the VFA by CT.. In patients with T2D without elevated BNP > 100 pg/mL as indicator for fluid accumulation interfering with BIA, estimation of the VFA by dual BIA significantly correlated with that by CT and also detected comorbid hypertension and/or dyslipidemia with T2D equivalent to those detected by CT. Hence, dual BIA could be an alternative to CT as a standard method for estimating the VFA in patients with diabetes.

Topics: Adiposity; Aged; Biomarkers; Cardiovascular Diseases; Comorbidity; Diabetes Mellitus, Type 2; Dyslipidemias; Electric Impedance; Female; Humans; Hypertension; Intra-Abdominal Fat; Japan; Male; Middle Aged; Natriuretic Peptide, Brain; Obesity; Predictive Value of Tests; Prevalence; Reproducibility of Results; Risk Factors; Tomography, X-Ray Computed

Topics: Aged; Bayes Theorem; Biomarkers; Case-Control Studies; Diabetes Mellitus, Type 2; Female; Glomerular Filtration Rate; Hepatitis A Virus Cellular Receptor 1; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Renal Insufficiency, Chronic

High-sensitivity troponin I (hs-Tnl) and B-type natriuretic peptide (BNP) are promising prognostic markers for coronary artery disease (CAD). This prospective cohort study investigated whether a combination of these cardiac biomarkers with conventional risk factors would add incremental value for the prediction of secondary major adverse cardiovascular events (MACEs) in patients with CAD, with and without type 2 diabetes mellitus (T2DM).. Baseline plasma level of hs-Tnl and BNP was measured in 2275 Chinese patients with stable CAD. Patients were monitored for new-onset of MACE over a median of 51 months. Cox proportional hazard model and area under the receiver operating characteristic curve (AUC) were used to assess the association of cardiac biomarkers with MACE and their predictive values in relationship with or without T2DM.. During the follow up period 402 (18%) patients experienced a new-onset MACE with hs-Tnl and BNP level significantly higher than in those without MACE. In multivariable analyses, patients with elevated hs-Tnl (hazard ratio, 1.75 [95% CI 1.41-2.17]; P < 0.001) and BNP (hazard ratio, 1.42 [95% CI 1.15-1.75]; P = 0.001) were significantly associated with an increased risk of MACE after adjustment for variables of a risk factor model of age, sex, T2DM and hypertension. The risk factor model had an AUC of 0.64 for MACE prediction. The AUC significantly increased to 0.68 by the addition of hs-Tnl to the risk factor model. Subgroup analyses showed that hs-Tnl and BNP remained significant predictors of MACE in both patients with and without T2DM in multivariable models with higher risk of MACE evident in those without T2DM. Among patients without T2DM, addition of each biomarker yielded greater predictive accuracy than in T2DM patients, with AUC further increased to 0.75 when a combination of hs-Tnl and BNP was added to the risk factor model (age, sex and hypertension).. Elevated hs-Tnl and BNP level are independent predictors of new-onset MACE in CAD patients, irrespective of diabetes status. Among CAD patients without T2DM, a combination of cardiac biomarkers hs-Tnl and BNP yield the greatest predictive value beyond conventional risk factors.

Topics: Aged; Biomarkers; Cardiovascular Diseases; Coronary Artery Disease; Diabetes Mellitus, Type 2; Female; Hong Kong; Humans; Incidence; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Progression-Free Survival; Prospective Studies; Risk Assessment; Risk Factors; Time Factors; Troponin I; Up-Regulation

Sodium glucose transporter 2 inhibitors (SGLT2is), new antidiabetic agents, were reported to improve not only glycemic parameters but also metabolic and circulatory parameters. Whereas, several adverse events caused by SGLT2is were also reported. We aimed to investigate the changes of glycemic, metabolic, and circulatory parameters as well as safety with low-dose administration of two SGLT2is, canagliflozin and ipragliflozin, and also the difference between the two agents. 25 individuals with type-2 diabetes mellitus (T2DM) were recruited and administered with low-dose SGLT2is, canagliflozin (n = 10, 50 mg/day) and ipragliflozin (n = 15, 25 mg/day). We examined glycemic, metabolic, and circulatory parameters at baseline and 24 weeks after administration. All patients completed the study without complications. Compared with baseline, levels of glycated hemoglobin, fasting plasma glucose, and homeostasis model assessment of β-cell function improved significantly at 24 weeks after administration (p < 0.05). Levels of body weight, low-density lipoproteincholesterol, aspartate transaminase, γ-glutamyl transferase, and urinary excretion of albumin also improved significantly (p < 0.05). Moreover, systolic/diastolic blood pressure and levels of brain natriuretic peptide improved significantly (p < 0.05). The comparison of improvement ratio (values of improvement/values of basement) of each agent revealed that there was a significant difference between low-dose canagliflozin and low-dose ipragliflozin for brain natriuretic peptide (0.4404 vs. 0.0970, p = 0.0275). Hence, low-dose SGLT2is could be useful for patients of T2DM not only for hyperglycemia but also for metabolic and circulatory disorders without eliciting adverse events. In addition, with regard to the efficacy upon cardiovascular function, canagliflozin could be more suitable than ipragliflozin.

Topics: Aged; Blood Glucose; Blood Pressure; Canagliflozin; Diabetes Mellitus, Type 2; Drug Administration Schedule; Female; Glucosides; Glycated Hemoglobin; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Sodium-Glucose Transporter 2 Inhibitors; Thiophenes

Topics: Aged; Biomarkers; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Hand Strength; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Retrospective Studies; Survival Analysis

Arginine vasopressin (AVP), which induces vasoconstriction and conserves solute-free water when released during high plasma osmolality, is secreted through 2 mechanisms: osmoregulation and baroregulation. This study aims to clarify the mechanisms and influencing factors for non-osmotic AVP secretion in adult patients with congenital heart disease (CHD). AVP levels were measured in 74 adults with CHD. Non-osmotic AVP secretion was defined as excessive AVP secretion relative to the AVP level inferred from plasma osmolality. Accordingly, 10 patients (13.5%) demonstrated non-osmotic AVP secretion, with AVP levels higher than those in patients without non-osmotic AVP secretion (6.4 ± 3.1 vs. 1.6 ± 0.9 pg/ml; p < 0.0001). Non-osmotic AVP secretion was significantly correlated with diuretic use [odds ratio (OR) 7.227; confidence interval (CI) 1.743-29.962; p = 0.0006], HbA1c level (OR 11.812; CI 1.732-80.548; p = 0.012), and B-type natriuretic peptide (BNP) level (OR 1.007; CI 1.001-1.012; p = 0.022). Multiple logistic regression analysis revealed that there was a significant association between non-osmotic AVP secretion and HbA1c level (OR 9.958; 1.127-87.979; p = 0.0039), and a nearly significant relationship between non-osmotic AVP secretion and BNP (OR 1.006; CI 1.000-1.012; p = 0.056). In conclusion, this study showed that 13.5% of adult patients with CHD demonstrated non-osmotic AVP secretion, which could be correlated with heart failure and insulin resistance. The AVP system might be one of the mechanisms linking heart failure and the onset of type 2 diabetes mellitus in adults with CHD.

Topics: Adult; Arginine Vasopressin; Biomarkers; Diabetes Mellitus, Type 2; Disease Progression; Female; Glycated Hemoglobin; Heart Defects, Congenital; Heart Failure; Humans; Logistic Models; Male; Middle Aged; Natriuretic Peptide, Brain; Young Adult

Natriuretic peptides (NPs) have emerged as important regulators of lipid metabolism. Reduced levels of NPs are reported in obesity and in patients with type 2 diabetes (T2D). This NP deficiency may affect their ectopic fat distribution and lead to high risk of non-alcoholic fatty liver disease (NAFLD).. In this cross-sectional study, the association between N-terminal pro-B-type natriuretic peptide (NT-proBNP) and liver fat content was quantified using 1H-magnetic resonance spectroscopy in 120 patients with T2D.. Reduced plasma NT-proBNP levels are independently associated with high liver fat content in patients with T2D. The present study suggests that NP deficiency may play a role in the development of NAFLD in T2D.

Topics: Absorptiometry, Photon; Adipose Tissue; Aged; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Female; Humans; Liver; Magnetic Resonance Spectroscopy; Male; Middle Aged; Natriuretic Peptide, Brain; Non-alcoholic Fatty Liver Disease; Peptide Fragments

In asymptomatic patients with type 2 diabetes (T2D), the prevalence of silent myocardial infarction on routine electrocardiograms is about 4% while for silent myocardial ischemia it is 20-30%. Some studies showed that silent myocardial infarction is associated with an increased risk of incident heart failure (HF), whereas no prospective study has ever reported such a risk in patients with silent myocardial ischemia. In patients with HF, however, previously unrecognized coronary artery disease (CAD) often seems to be involved. Brain natriuretic peptide (BNP) and N‑terminal pro-BNP (NT-proBNP) levels represent first-line diagnostic tools for patients with suspected HF and might also serve as biomarkers for silent CAD. Echocardiography provides a detailed report of cardiac alterations that includes changes suggestive of ischemia, heart failure, and left ventricular dysfunction in addition to strong prognostic indices. Diabetic patients with silent myocardial infarction or silent myocardial ischemia should be screened for asymptomatic changes in left ventricular function or structure. In patients with silent CAD, all risk factors need to be better controlled and the choice of antihyperglycemic agents adjusted. In patients with congestive HF and no obvious cause of HF, invasive coronary angiography (or noninvasive computed tomography angiography) should be performed to detect CAD, since the finding of CAD may involve revascularization and requires additional treatments including antiplatelet agents and statins. Future research is needed to examine the cost effectiveness of screening for silent myocardial ischemia as part of HF risk assessment, and to identify preventive therapies to lower the risk of HF among patients with silent myocardial infarction.

Topics: Biomarkers; Coronary Artery Disease; Diabetes Mellitus, Type 2; Heart Failure; Humans; Myocardial Infarction; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Risk Factors

The presence of concomitant Type II diabetic mellitus (T2DM) and depressive symptoms adversely affects individuals with symptomatic heart failure (HF).. In presymptomatic stage B HF, this study hypothesized the presence of greater inflammation and depressive symptoms in T2DM as compared to non-T2DM Stage B patients.. This cross-sectional study examined clinical parameters, inflammatory biomarkers, and depressive symptoms in 349 T2DM and non-T2DM men with asymptomatic stage B HF (mean age 66.4 years ±10.1; range 30-91).. Fewer diabetic HF patients had left ventricular (LV) systolic dysfunction (P < .05) although more had LV diastolic dysfunction (P < .001). A higher percentage of T2DM HF patients were taking ACE-inhibitors, beta-blockers, calcium channel blockers, statins, and diuretics (P values < .05). T2DM HF patients had higher circulating levels of interleukin-6 (IL-6) (P < .01), tumor necrosis factor-alpha (P < .01), and soluble ST2 (sST2) (P < .01) and reported more somatic/affective depressive symptoms (Beck Depression Inventory II) (P < .05) but not cognitive/affective depressive symptoms (P = .20). Among all patients, in a multiple regression analysis predicting presence of somatic/affective depressive symptoms, sST2 (P = .026), IL-6 (P = .010), B-type natriuretic peptide (P = .016), and sleep (Pittsburgh Sleep Quality Index [P < .001]) were significant predictors (overall model F = 15.39, P < .001, adjusted R. Somatic/affective but not cognitive/affective depressive symptoms are elevated in asymptomatic HF patients with T2DM patients. Linkages with elevated inflammatory and cardiac relevant biomarkers suggest shared pathophysiological mechanisms among T2DM HF patients with somatic depression, and these conditions are responsive to routine interventions, including behavioral. Copyright © 2019 John Wiley & Sons, Ltd.

Topics: Aged; Asymptomatic Diseases; Biomarkers; Blood Glucose; Comorbidity; Cross-Sectional Studies; Depression; Diabetes Mellitus, Type 2; Disease Progression; Echocardiography; Female; Follow-Up Studies; Heart Failure; Humans; Interleukin-6; Male; Natriuretic Peptide, Brain; Risk Factors; Survival Rate; Tumor Necrosis Factor-alpha; United States

A plethora of studies have demonstrated that cardiomyopathy represents a serious source of morbidity and mortality in patients with diabetes. Yet, the underlying mechanisms of diabetic cardiomyopathy are still poorly understood. Of interest, cytochrome P450 2J (CYP2J) and soluble epoxide hydrolase (sEH) are known to control the maintenance of cardiovascular health through the regulation of cardioprotective epoxyeicosatrienoic acids (EETs) and its less active products, dihydroxyeicosatrienoic acids (DHETs). Therefore, we examined the role of the aforementioned pathway in the development of diabetic cardiomyopathy. Our diabetic model initiated cardiomyopathy as indexed by the increase in the expression of hypertrophic markers such as NPPA. Furthermore, diabetic cardiomyopathy was associated with a low level of cardiac EETs and an increase of the DHETs/EETs ratio both in vivo and in cardiac cells. The modulation in EETs and DHETs was attributed to the increase of sEH and the decrease of CYP2J. Interestingly, the reduction of sEH attenuates cardiotoxicity mediated by high glucose in cardiac cells. Mechanistically, the beneficial effect of sEH reduction might be due to the decrease of phosphorylated ERK1/2 and p38. Overall, the present work provides evidence that diabetes initiates cardiomyopathy through the increase in sEH, the reduction of CYP2J, and the decrease of cardioprotective EETs.

Topics: Animals; Atrial Natriuretic Factor; Blood Glucose; Cell Line; Cytochrome P-450 Enzyme System; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Diabetic Cardiomyopathies; Diet, High-Fat; Eicosanoids; Epoxide Hydrolases; Extracellular Signal-Regulated MAP Kinases; Humans; Male; Mice, Inbred C57BL; Myocytes, Cardiac; Natriuretic Peptide, Brain; Obesity; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Signal Transduction; Streptozocin

Topics: Blood Pressure; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Glucose; Heart Failure; Humans; Hypertension; Natriuretic Peptide, Brain; Registries; Risk Factors; Sodium

Optimal blood pressure for prevention of cardiovascular (CV) events in patients with Type 2 diabetes mellitus (T2DM) remains uncertain and there is concern for increased risk with low diastolic blood pressure (DBP). This study analysed the association between blood pressure and CV outcomes in high-risk patients with T2DM.. Patients with T2DM and elevated CV risk were enrolled in the Saxagliptin Assessment of Vascular Outcomes Recorded in patients with diabetes mellitus-Thrombolysis in Myocardial Infarction 53 trial. Cardiovascular outcomes were compared in the biomarker subgroup (n = 12 175) after stratification by baseline systolic blood pressure (SBP) and DBP. Adjusted risk was calculated by blood pressure stratum using clinical covariates plus N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin-T (hsTnT). Trends were tested using linear and quadratic models. Adjusted risk of the composite endpoint of CV death, myocardial infarction (MI), or ischaemic stroke showed U-shaped relationships with baseline SBP and DBP (Pquadratic ≤ 0.01) with nadirs at SBP 130-140 or DBP 80-90 mmHg. Diastolic blood pressure <60 mmHg was associated with increased risk of MI (adjusted hazard ratio 2.30; 95% confidence interval 1.50-3.53) relative to DBP 80-90 mmHg. Adjusted odds of hsTnT concentration ≥14 ng/L showed U-shaped relationships with SBP and DBP (Pquadratic ≤ 0.01). The relationships between low DBP, elevated hsTnT, and increased MI remained after exclusion of patients with prior heart failure or NT-proBNP >median, suggesting that the relationship was not due to confounding from diagnosed or undiagnosed heart failure.. In patients with diabetes and elevated CV risk, even after extensive adjustment for underlying disease burden, there was a persistent association for low DBP with subclinical myocardial injury and risk of MI.

Topics: Aged; Antihypertensive Agents; Blood Pressure; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Diastole; Female; Humans; Hypertension; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Patient Care Planning; Peptide Fragments; Stroke; Systole; Troponin T

Topics: Diabetes Mellitus, Type 2; Erythrocytes; Heart Failure; Humans; Lymphocyte Count; Natriuretic Peptide, Brain

Patients with non-valvular atrial fibrillation (AF) and a high risk for oral anticoagulation can be treated by percutaneous implantation of left atrial appendage occlusion devices (LAAC) to reduce the risk of cardio-embolic stroke. This study evaluates whether LAAC may influence lipid metabolism, which has never been investigated before. Patients with successful LAAC were included consecutively. Venous peripheral blood samples of patients were collected immediately before (T0, baseline) and 6 months after (T1, mid-term) LAAC. A targeted metabolomics approach based on electrospray ionization liquid chromatography-mass spectrometry (ESI-LC-MS/MS) and MS/MS measurements was performed. A total of 34 lipids revealed a significant change from baseline to mid-term follow-up after successful LAAC. Subgroup analysis revealed confounding influence by gender, age, diabetes mellitus type II, body mass index, left ventricular ejection fraction, creatinine and NT-proBNP. After multivariable adjustment within logistic regression models, these 34 lipids were still significantly altered after LAAC. Successful percutaneous LAAC may affect lipid metabolism and thereby may potentially affect pro-atherogenic and cardio-toxic effects.

Topics: Age Factors; Aged; Aged, 80 and over; Atrial Appendage; Atrial Fibrillation; Body Mass Index; Creatinine; Diabetes Mellitus, Type 2; Echocardiography, Transesophageal; Female; Humans; Lipid Metabolism; Lipids; Logistic Models; Male; Metabolome; Natriuretic Peptide, Brain; Peptide Fragments; Percutaneous Coronary Intervention; Prospective Studies; Risk Factors; Sex Factors; Spectrometry, Mass, Electrospray Ionization; Stroke Volume; Tandem Mass Spectrometry

Analyzing the relationships between biomarkers representing distinct pathophysiologic pathways and microalbuminuria (MA) can strengthen the identifying ability for renal damage and illuminate previously unrecognized pathways for the pathogenesis of renal damage. The current analysis was to clarify the associations between biomarkers, including N-terminal prohormone of brain natriuretic peptide (NT-proBNP), high-sensitivity C-reactive protein (hsCRP), homocysteine and uric acid (UA), and MA in Chinese middle-aged and elderly from communities.. All 839 residents had complete set of these biomarkers and full assessment of MA.. Prevalence of participants with MA was 13.5% (113 participants). Levels of age, systolic blood pressure (SBP), fasting blood glucose (FBG), homocysteine and NT-proBNP and proportion of cigarette smoking in participants with MA significantly exceeded those in participants without MA (p < 0.05 for all). In single-marker and multi-marker models of linear and logistic regression analyses, homocysteine and NT-proBNP levels (p < 0.05 for all) rather than hsCRP and UA levels (p > 0.05 for all) were statistically significant in relation to MA. Additionally, no matter which biomarker was directed at, levels of age, SBP and FBG and proportion of cigarette smoking had significant associations with MA. Homocysteine and NT-proBNP levels (p < 0.05 for all) rather than hsCRP and UA levels (p > 0.05 for all) had significant abilities to identify MA.. Both single-marker and multi-marker analyses confirmed that homocysteine and NT-proBNP were associated with MA in Chinese middle-aged and elderly from communities after adjustment for multiple confounders.

Topics: Aged; Aged, 80 and over; Albuminuria; Biomarkers; C-Reactive Protein; China; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Female; Homocysteine; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Risk Factors; Smoking; Uric Acid

Previous studies revealed the association between serum Nterminal pro-brain natriuretic peptide (NT-proBNP) level and chronic kidney diseases (CKD) in general population. However, little is known about the association between serum NT-proBNP level and incident CKD in patients with type 2 diabetes. Thus, we investigated the impact of serum NT-proBNP level on incident CKD in patients with type 2 diabetes.. We enrolled 211 type 2 diabetic patients without CKD in this cohort study. CKD was diagnosed as estimated glomerular filtration rate <60 ml/min/1.73 m2. We divided the patients into three groups according to the tertiles of serum NT-proBNP level. Univariates and multivariate hazard ratios (HRs) for the incident CKD were calculated by Cox regression analyses.. Over the median follow-up period of 7 years, 56 patients developed incident CKD. Log NTproBNP was positively associated with incident CKD (HR 3.70, 95%CI 1.72-8.18, p <0.001). Compared with the lowest level of serum NT-proBNP tertile (≤36 pg/mL), the highest level of serum NTproBNP tertile (≥84 pg/mL) showed increased risk of incident CKD after adjusting age, sex, body mass index, hemoglobin A1c, creatinine, smoking, usage of hypertension drug and urinary albumin excretion at baseline examination (adjusted HR2.37, 95% CI 1.09-5.48, p = 0.028).. Serum NT-proBNP level is an independent biomarker for incident CKD in patients with type 2 diabetes.

Topics: Aged; Biomarkers; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Disease Progression; Female; Humans; Incidence; Japan; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Renal Insufficiency, Chronic; Retrospective Studies; Risk Factors; Time Factors

Developing sparse panels of biomarkers for cardiovascular disease in type 2 diabetes would enable risk stratification for clinical decision making and selection into clinical trials. We examined the individual and joint performance of five candidate biomarkers for incident cardiovascular disease (CVD) in type 2 diabetes that an earlier discovery study had yielded.. Apolipoprotein CIII (apoCIII), N-terminal prohormone B-type natriuretic peptide (NT-proBNP), high sensitivity Troponin T (hsTnT), Interleukin-6, and Interleukin-15 were measured in baseline serum samples from the Collaborative Atorvastatin Diabetes trial (CARDS) of atorvastatin versus placebo. Among 2105 persons with type 2 diabetes and median age of 62.9 years (range 39.2-77.3), there were 144 incident CVD (acute coronary heart disease or stroke) cases during the maximum 5-year follow up. We used Cox Proportional Hazards models to identify biomarkers associated with incident CVD and the area under the receiver operating characteristic curves (AUROC) to assess overall model prediction.. Three of the biomarkers were singly associated with incident CVD independently of other risk factors; NT-proBNP (Hazard Ratio per standardised unit 2.02, 95% Confidence Interval [CI] 1.63, 2.50), apoCIII (1.34, 95% CI 1.12, 1.60) and hsTnT (1.40, 95% CI 1.16, 1.69). When combined in a single model, only NT-proBNP and apoCIII were independent predictors of CVD, together increasing the AUROC using Framingham risk variables from 0.661 to 0.745.. The biomarkers NT-proBNP and apoCIII substantially increment the prediction of CVD in type 2 diabetes beyond that obtained with the variables used in the Framingham risk score.

Topics: Adult; Aged; Apolipoprotein C-III; Biomarkers; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Female; Humans; Incidence; Interleukin-15; Interleukin-6; Ireland; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Randomized Controlled Trials as Topic; Reproducibility of Results; Risk Assessment; Risk Factors; Time Factors; Troponin T; United Kingdom

This study aimed to evaluate cardiac function and compare the concentration of cardiac biomarkers including cardiac troponin I (cTnI), galectin-3 (Gal-3), and N-terminal pro B-type natriuretic peptides (NT-proBNP) in diabetic and control dogs.. Thirty-nine dogs were included. The diabetic and control groups consisted of 19 and 20 dogs, respectively.. Plasma cTnI, Gal-3, and NT-proBNP concentrations were measured in the diabetic and control groups. Echocardiography was performed in all dogs to evaluate cardiac structure and function. Echocardiographic values and cardiac biomarker concentrations between the two groups were compared with the Mann-Whitney U test. The p-value < 0.05 was considered statistical significance.. No evidence of cardiac structural changes was detected in diabetic dogs on two-dimensional echocardiography. The echocardiographic values of diabetic and control dogs were within reference intervals. Echocardiographic changes indicating diastolic dysfunction assessed by spectral flow Doppler echocardiography and tissue Doppler imaging were found in diabetic dogs (42.10%) compared with control dogs (10.00%; p = 0.022). Diabetic dogs with durations of diabetes mellitus > 1 year had an increased left ventricular wall thickness and echocardiographic changes suggesting diastolic dysfunction compared with those with duration of diabetes mellitus < 1 year. No evidence of systolic dysfunction was detected in diabetic dogs. No significant difference in plasma cTnI, Gal-3, and NT-proBNP concentrations was found between the two groups.. Echocardiographic changes suggested that left ventricular diastolic dysfunction was detected in diabetic dogs without changes in the concentration of cardiac biomarkers including cTnI, Gal-3, and NT-proBNP compared with the age- and breed-matched control dogs.

Topics: Animals; Biomarkers; Case-Control Studies; Diabetes Mellitus, Type 2; Dog Diseases; Dogs; Echocardiography; Female; Galectin 3; Male; Natriuretic Peptide, Brain; Peptide Fragments; Sensitivity and Specificity; Troponin I; Ventricular Dysfunction, Left

N-terminal pro-B-type natriuretic peptide (NT-proBNP) is the gold standard prognostic biomarker for diagnosis and occurrence of heart failure. Here, we compared its prognostic value for the occurrence of congestive heart failure with that of plasma mid-region pro-adrenomedullin (MR-proADM), a surrogate for adrenomedullin, a vasoactive peptide with vasodilator and natriuretic properties, in people with type 2 diabetes.. Plasma MR-proADM concentration was measured in baseline samples of a hospital-based cohort of consecutively recruited participants with type 2 diabetes. Our primary endpoint was heart failure requiring hospitalisation.. We included 1438 participants (age 65 ± 11 years; 604 women and 834 men). Hospitalisation for heart failure occurred during follow-up (median 64 months) in 206 participants; the incidence rate of heart failure was 2.5 (95% CI 2.2, 2.9) per 100 person-years. Plasma concentrations of MR-proADM and NT-proBNP were significantly associated with heart failure in a Cox multivariable analysis model when adjusted for age, diabetes duration, history of coronary heart disease, proteinuria and baseline eGFR (. MR-proADM is a prognostic biomarker for heart failure in people with type 2 diabetes but gives no significant complementary information on prediction of heart failure compared with NT-proBNP.

Topics: Adrenomedullin; Aged; Biomarkers; Diabetes Mellitus, Type 2; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Neuropeptides; Peptide Fragments; Prognosis; Prospective Studies

Renal dysfunction is a key risk factor for all-cause mortality in patients with type 2 diabetes (T2D). Special attention has been raised regarding the role of soluble tumor necrosis factor receptor1 (sTNFR1) and brain natriuretic peptide (BNP) in diabetic nephropathy (DN) since they play a crucial role in the pathogenesis of T2D complications. Elevated concentrations of sTNFR1and BNP were found to be associated with progression to end stage renal disease (ESRD) in T2D. We determined serum levels of sTNFR1 and BNP in T2D patients and correlated them with various clinical variables especially kidney function and urinary albumin creatinine ratio (UACR). This study included 30 patients with T2D who were divided into two groups according to estimated glomerular filtration rate (eGFR): group 1with (eGFR < 60 mL/min/1.73m²) and group 2 with (eGFR > 60 mL/min/1.73 m²). They were compared with 15 sexes and age matched healthy individuals as a control group. Serum levels of sTNFR1 and BNP were determined using ELISA. Serum levels of sTNFR1 and BNP were significantly higher in group1when compared with group 2 (P= 0.000, P= 0.000) and they were significantly higher in both group1 and group 2 as compared with control (P= 0.000, P= 0.000); (P= 0.000, P = 0.000) respectively. Both sTNFR1 and BNP levels showed significant negative correlation with eGFR (r = - 0.58, P = 0.000); (r= - 0.77, P= 0.000) respectively, and significant positive correlation with UACR (r= 0.84, P= 0.000); (r=0.80, P= 0.000) respectively. In conclusion, increased circulating levels of sTNFR1 and BNP were associated with loss of kidney function in T2D patients.

Topics: Case-Control Studies; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Egypt; Glomerular Filtration Rate; Humans; Natriuretic Peptide, Brain; Receptors, Tumor Necrosis Factor, Type I

We investigated whether biochemical cardiovascular risk factors and/or markers of subclinical cardiovascular disease were associated with the development of reduced renal function in people with type 2 diabetes.. A cohort of 1066 Scottish men and women aged 60-74 years with type 2 diabetes from the Edinburgh Type 2 Diabetes Study were followed up for a median of 6.7 years. New-onset reduced renal function was defined as two eGFRs <60 ml. A total of 119 participants developed reduced renal function during follow-up. ABI, PWV, NT-proBNP and hsTnT were all associated with onset of decline in renal function following adjustment for age and sex. These associations were attenuated after adjustment for additional diabetes renal disease risk factors (systolic BP, baseline eGFR, albumin:creatinine ratio and smoking pack-years), with the exception of hsTnT which remained independently associated (HR 1.51 [95% CI 1.22, 1.87]). Inclusion of hsTnT in a predictive model improved the continuous net reclassification index by 0.165 (0.008, 0.286).. Our findings demonstrate an association between hsTnT, a marker of subclinical cardiac ischaemia, and subsequent renal function decline. Further research is required to establish the predictive value of hsTnT and response to intervention.

Topics: Aged; Biomarkers; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Female; Glomerular Filtration Rate; Humans; Kidney; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Proportional Hazards Models; Pulse Wave Analysis; Risk Factors; Troponin T

This study examined the individual and combined effect of N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T (hs-cTnT), interleukin-6 (IL-6), and hs-CRP on the prediction of heart failure incidence or progression in patients with type 2 diabetes.. A nested case-cohort study was conducted in 3,098 participants with type 2 diabetes in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial.. A higher value of each biomarker was significantly associated with a higher risk of heart failure incidence or progression, after adjustment for major risk factors. The hazard ratios per 1-SD increase were 3.06 (95% CI 2.37, 3.96) for NT-proBNP, 1.50 (1.27, 1.77) for hs-cTnT, 1.48 (1.27, 1.72) for IL-6, and 1.32 (1.12, 1.55) for hs-CRP. The addition of NT-proBNP to the model including conventional risk factors meaningfully improved 5-year risk-predictive performance (C statistic 0.8162 to 0.8800; continuous net reclassification improvement [NRI] 73.1%; categorical NRI [<5%, 5-10%, >10% 5-year risk] 24.2%). In contrast, the addition of hs-cTnT, IL-6, or hs-CRP did not improve the prediction metrics consistently in combination or when added to NT-proBNP.. Only NT-proBNP strongly and consistently improved the prediction of heart failure in patients with type 2 diabetes beyond a wide range of clinical risk factors and biomarkers.

Topics: Aged; Biomarkers; C-Reactive Protein; Cholesterol; Cohort Studies; Diabetes Mellitus, Type 2; Disease Progression; Female; Follow-Up Studies; Glycated Hemoglobin; Heart Failure; Humans; Incidence; Interleukin-6; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Risk Factors; Sample Size; Triglycerides; Troponin T

To investigate the associations of sleep duration with all-cause mortality, glycemic control, and other clinical parameters of patients with type 2 diabetes.. From April 2013 to December 2015, we conducted a retrospective cohort study. Study participants were divided into three groups according to their sleep duration. Multiple regression analysis and Cox proportional hazards analysis were performed to assess the independent associations of sleep duration with clinical parameters and all-cause mortality.. We enrolled 1233 patients who were then followed for 860 ± 264 days. During the follow-up period, 20 patients (1.6%) died. Sleep duration inversely associated with plasma B-type natriuretic peptide levels (β = -0.203, p = 0.012) in short (<7 h) sleepers, whereas it was positively associated with hemoglobin A1c levels (β = 0.156, p = 0.021) in long (≥9 h) sleepers. Moreover, Cox proportional hazard analysis revealed that short sleep duration was a significant predictor of all-cause mortality (hazard ratio = 0.473; confidence interval 0.248-0.905, p = 0.024).. Short sleep duration may serve as a prognostic indicator of mortality in Japanese patients with type 2 diabetes and may increase cardiovascular stress. Adequate sleep is essential for the management of type 2 diabetes.

Topics: Biomarkers; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Humans; Japan; Male; Middle Aged; Natriuretic Peptide, Brain; Prognosis; Proportional Hazards Models; Retrospective Studies; Sleep; Time Factors

We aimed at comparing the impact of multiple non-traditional biomarkers (ankle brachial pressure index (ABI), N-terminal pro-brain natriuretic peptide (NT-proBNP), high sensitivity cardiac troponin (hs-cTnT), gamma-glutamyl transpeptidase (GGT) and four markers of systemic inflammation), both individually and in combination, on cardiovascular risk prediction, over and above traditional risk factors incorporated in the QRISK2 score, in older people with type 2 diabetes.. We conducted a prospective study of 1066 men and women aged 60-75 years with type 2 diabetes mellitus, living in Lothian, Scotland.. After 8 years, 205 cardiovascular events occurred. Higher levels of hs-cTNT and NT-proBNP and lower ABI at baseline were associated with increased risk of CV events, independently of traditional risk factors (basic model). The C statistic of 0.722 (95% CI 0.681, 0.763) for the basic model increased on addition of individual biomarkers, most markedly for hs-cTnT (0.732; 0.690, 0.774)). Models including different combinations of biomarkers had even greater C statistics, with the highest for ABI, hs-cTnT and GGT combined (0.740; 0.699, 0.781).. Individually, hs-cTnT appeared to be the most promising biomarker in terms of improving vascular risk prediction in people with type 2 diabetes, over and above traditional risk factors incorporated in the QRISK2 score. Combining several non-traditional biomarkers added further predictive value, and this approach merits further investigation when developing cost effective risk prediction tools for use in clinical practice.

Topics: Aged; Ankle Brachial Index; Biomarkers; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Female; gamma-Glutamyltransferase; Humans; Incidence; Inflammation Mediators; Longitudinal Studies; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Prospective Studies; Risk Assessment; Risk Factors; Scotland; Time Factors; Troponin T

Objective Inflammatory cytokines generated in visceral fat have been shown to contribute to the development of insulin resistance. The involvement of pulmonary inflammation in insulin resistance remains unclear, but smoking is known to be a risk factor for diabetes as well as chronic obstructive pulmonary disease. We herein examined the hypothesis that increased serum levels of lung interstitial injury biomarkers [surfactant protein (SP)-A, SP-D and Krebs von den Lungen (KL)-6] are associated with the risk of diabetes development. Methods For cross-sectional and longitudinal analyses, we enrolled 750 apparently healthy non-diabetic subjects who received annual examinations in 2011 or 2012 in the Tanno-Sobetsu cohort. Results A cross-sectional analysis showed that distinct clinical parameters were associated with SP-A, SP-D and KL-6. In a multiple regression analysis, independent explanatory variables were Brinkman index and brain natriuretic peptide (BNP) for SP-A, sex (women), BNP and body mass index (BMI) for SP-D, and age and BMI for KL-6. A longitudinal analysis of 415 subjects who received annual examinations in both 2011 and 2014 showed that 13 (3.1%) of the patients developed type 2 diabetes during the 3-year follow-up. A multiple logistic regression analysis showed the KL-6 levels, systolic blood pressure and homeostasis model assessment of insulin resistance (HOMA-IR) in 2011 to be independently associated with new-onset diabetes. In a multiple regression analysis for HOMA-IR in 2014, the KL-6 level and BMI in 2011 were selected as explanatory variables. Conclusion A modest elevation of the serum KL-6 level is therefore considered to be associated with the risk for insulin resistance development and new-onset diabetes mellitus in a general population.

Topics: Age Factors; Aged; Aged, 80 and over; Biomarkers; Body Mass Index; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Female; Humans; Insulin Resistance; Longitudinal Studies; Male; Middle Aged; Mucin-1; Natriuretic Peptide, Brain; Pulmonary Surfactant-Associated Protein A; Pulmonary Surfactant-Associated Protein D; Risk Factors; Sex Factors

Topics: Acute Coronary Syndrome; Aged; Biomarkers; Diabetes Mellitus, Type 2; Female; Heart Failure; Hospitalization; Humans; Hypoglycemic Agents; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Peptides; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Up-Regulation

Myotonic dystrophy type 1 (DM1) and type 2 (DM2) are dominant inherited muscular dystrophies with multiple systemic involvement, often producing cardiac injury. This study sought to determine the clinical significance of elevated high sensitivity cardiac troponin T and I (hs-cTnT and hs-cTnI), and N-terminal pro B-type natriuretic peptide (NT-pro-BNP) in this population.. Sixty DM patients (35 men and 25 women; mean age: 45.1 years, range: 12-73 years) underwent clinical cardiac investigations and measurements of serum hs-cTnT, hs-cTnI, creatine kinase (CK), and NT-proBNP. Left ventricular (LV) ejection fraction (EF) was assessed by echocardiography.. Genetic analysis revealed that 46 of the 60 patients were DM1, and 14 DM2. Blood measurements showed persistent elevation of hs-cTnT and CK in 55/60 DM patients (91.73%). In contrast, hs-cTnI values were persistently normal throughout the study. Only 2 patients showed an EF <50%, being the overall range of this population between 40% and 79%. We found ECG abnormalities in 19 patients. Of these patients, 13 showed first or second-degree atrio ventricular (AV) blocks (PR interval ≥ 200 ms), 4 showed a left bundle branch block (LBBB) prolonged (QRS duration ≥120 ms), and 2 had an incomplete bundle branch block (QRS duration between 110 and 119 ms). After excluding patients with EF <50%, NT-pro-BNP measurement > 125 pg/mL was an independent predictor of ECG abnormalities.. NT-pro-BNP levels may be considered to be used clinically to identify DM patients at increased risk of developing myocardial conduction abnormalities.

Topics: Adolescent; Adult; Aged; Alleles; Biomarkers; Child; Cohort Studies; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Electrocardiography; Female; Heart Diseases; Humans; Male; Middle Aged; Myotonic Dystrophy; Natriuretic Peptide, Brain; Outpatients; Peptide Fragments; Prognosis; Protein Domains; Registries; Regression Analysis; Troponin I; Troponin T; Young Adult

Sleep-disordered breathing (SDB) is highly prevalent in patients with diabetes mellitus (DM) and heart failure (HF) and contributes to poor cardiovascular outcomes. Enlarged glycemic variability (GV) is a risk factor of cardiac events independently of average blood glucose level, but the influence of SDB on GV is uncertain. In this study, we examined whether the impact of SDB on GV is modified by the presence of DM with or without HF.. Two hundred three patients (67.5±14.1 [SD] years old, 132 males) who were admitted to our institute for examination or treatment of DM and/or HF underwent continuous glucose monitoring and polysomnography. Both HbA1c (8.0±2.0 vs. 5.7±0.4%) and mean amplitude of glycemic excursion (MAGE, median: 95.5 vs. 63.5 mg/dl) were significantly higher in a DM group (n = 100) than in a non-DM group (n = 103), but apnea-hypopnea index (AHI: 29.0±22.7 vs. 29.3±21.5) was similar in the two groups. AHI was correlated with log MAGE in the non-DM group but not in the DM group, and multivariate regression analysis revealed that AHI was an independent variable for log MAGE in the non-DM group but not in the DM group. We then divided the non-DM patients into two subgroups according to BNP level (100 pg/ml). AHI was positively correlated with log MAGE (r = 0.74, p<0.001) in the non-DM low-BNP subgroup, but such a correlation was not found in the non-DM high-BNP subgroup. Continuous positive airway pressure (CPAP) reduced MAGE from 75.3 to 53.0 mg/dl in the non-DM group but did not reduce MAGE in the DM group.. Severity of SDB was associated with higher GV, but DM as well as HF diminished the contribution of SDB to GV. Treatment with CPAP was effective for reduction of GV only in patients without DM.

Topics: Aged; Blood Glucose; Blood Glucose Self-Monitoring; Continuous Positive Airway Pressure; Diabetes Mellitus, Type 2; Female; Humans; Male; Multivariate Analysis; Natriuretic Peptide, Brain; Regression Analysis; Respiration; Sleep; Sleep Apnea Syndromes

Topics: Aged; Diabetes Mellitus, Type 2; Female; Heart Failure; Humans; Hypoglycemic Agents; Male; Middle Aged; Natriuretic Peptide, Brain; Pioglitazone; Retrospective Studies; Thiazolidinediones; Weight Gain

We explored the prognostic value of three circulating candidate biomarkers-midregional-proadrenomedullin (MR-proADM), soluble tumor necrosis factor receptor 1 (sTNFR1), and N-terminal prohormone brain natriuretic peptide (NT-proBNP)-for change in renal function in patients with type 2 diabetes.. Outcomes were defined as renal function loss (RFL), ≥40% decline of estimated glomerular filtration rate (eGFR) from baseline, and rapid renal function decline (RRFD), absolute annual eGFR slope <-5 mL/min/year. We used a proportional hazard model for RFL and a logistic model for RRFD. Adjustments were performed for established risk factors (age, sex, diabetes duration, HbA. Among 1,135 participants (mean eGFR 76 mL/min, median uACR 2.6 mg/mmol, and median GFR slope -1.6 mL/min/year), RFL occurred in 397, RRFD developed in 233, and 292 died during follow-up. Each biomarker predicted RFL and RRFD. When combined, MR-proADM, sTNFR1, and NT-proBNP predicted RFL independently from the established risk factors (adjusted hazard ratio 1.59 [95% CI 1.34-1.89],. In addition to established risk factors, MR-proADM, sTNFR1, and NT-proBNP improve risk prediction of loss of renal function in patients with type 2 diabetes.

Topics: Adrenomedullin; Aged; Albumins; Biomarkers; Body Mass Index; Creatinine; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; France; Glomerular Filtration Rate; Humans; Kidney Diseases; Kidney Function Tests; Logistic Models; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Proportional Hazards Models; Prospective Studies; Receptors, Tumor Necrosis Factor, Type I; Risk Factors

To examine if a simple biomarker can identify people with diabetes who are at high risk of atrial fibrillation.. A retrospective cohort study was conducted at a single centre in people with Type 2 diabetes referred to our department between January 2000 and December 2007. In 517 consecutive people without any history, signs or symptoms of atrial fibrillation at baseline, the association between baseline B-type natriuretic peptide level and future atrial fibrillation incidence was examined, with adjustments for other potentially confounding factors.. A total of 28 people were diagnosed with new-onset atrial fibrillation during a median 6-year follow-up. When people were categorized into three groups according to B-type natriuretic peptide clinical thresholds (20 and 100 pg/ml), hazard ratios for the development of atrial fibrillation in the middle and highest B-type natriuretic peptide groups were 2.8 and 9.4, respectively, compared with the lowest B-type natriuretic peptide group. Time-dependent receiver-operating curve analysis identified a threshold for B-type natriuretic peptide to detect atrial fibrillation development of 52.8 pg/ml (sensitivity 75.2%, specificity 68.8%). The B-type natriuretic peptide predictive value was independent of and similar to that of left atrial size and ventricular dimension.. In people with Type 2 diabetes, high baseline B-type natriuretic peptide levels were significantly associated with future atrial fibrillation development.

Topics: Aged; Atrial Fibrillation; Cohort Studies; Diabetes Mellitus, Type 2; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Proportional Hazards Models; Retrospective Studies

The association between natriuretic peptides and clinical outcome in asymptomatic hypertensive and diabetic patients with no clinical evidence of heart failure (HF) is still unclear. We assessed the prognostic value of NT-pro BNP, and its interactions with age and gender, in a cohort of asymptomatic, stage A/B HF hypertensive and diabetic patients enrolled in primary care.. NT-proBNP was measured in 1012 asymptomatic subjects with systemic hypertension and/or type-2 diabetes (age 66.6 ± 7.8 years, 48 % males) with no clinical evidence of HF. Patients were prospectively followed over 49.8 ± 6.7 months for the development of cardiac death, HF hospitalization, and nonfatal myocardial infarction.. Patients with NT-proBNP above the 80th age- and gender-specific percentile showed a threefold risk of events as compared to those with NT-proBNP under this cut-off [hazard ratio 3.2 (2.6-8.3), p < 0.0001]. In multivariable analysis, NT-proBNP added independent and incremental prognostic information to a predictive model including established risk factors (p < 0.0001). After stratification by age, increased NT-proBNP predicted outcome among patients in the second and third age tertiles, but not among those in the first tertile. Increased NT-proBNP was associated with a 3.6-fold risk in women and a 2.9-fold risk in men. Addition of the gender-NT-proBNP interaction to prognostic models further improved prediction of events (p = 0.014).. NT-proBNP measurement adds independent and incremental information for the prediction of clinical outcome in asymptomatic, stage A-B HF hypertensive and diabetic patients taken from primary care. This prognostic value might be further evident in the elderly and among women.

Topics: Age Factors; Aged; Asymptomatic Diseases; Biomarkers; Chi-Square Distribution; Diabetes Mellitus, Type 2; Female; Humans; Hypertension; Italy; Kaplan-Meier Estimate; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Odds Ratio; Peptide Fragments; Predictive Value of Tests; Primary Health Care; Prognosis; Proportional Hazards Models; Prospective Studies; Risk Factors; Sex Factors; Time Factors

Clinical evaluation of patients with diabetes or after myocardial infarction (MI) with preserved left ventricular (LV) systolic function is not very precise in isolating patients at particularly high risk of developing manifest cardiac failure and associated cardiovascular incident. Early diagnosis of LV diastolic dysfunction is essential because implementation of the appropriate treatment can positively affect the course of the disease.. To assess the impact of LV diastolic function on B-type natriuretic peptide (BNP) concentration at rest and immediately after exercise test, and to search for the relationship between LV diastolic function and BNP secretion, tolerance, and duration of exercise in the studied groups of patients.. Ninety-nine consecutive patients were qualified for the study: in Group 1 - patients with type 2 diabetes without a history of MI, and in Group 2 - patients after MI with preserved LV systolic function (ejection fraction ≥ 40%), without diabetes. The studied patients had echocardiography with LV systolic and diastolic function evaluation, an electrocardiographic exercise test and blood sampling for BNP determination before and immediately after exercise test.. The study included 99 patients aged 40-75 years (60 patients after MI and 39 patients with diabetes). The study group included 62 patients who were diagnosed with diastolic dysfunction. Diastolic dysfunction occurred in 41 (68.4%) patients in the group after MI, and in 21 (53.8%) patients in the group with diabetes, severe disorders in the form of pseudonormal and restrictive mitral valve inflow occurred in 13 (21.7%) and five (12.8%), respectively. The average BNP concentration in patients with severe diastolic dysfunction at rest was 188.3 vs. 25.2 pg/mL in patients with normal diastolic function (p < 0.001). In all patients with severe diastolic dysfunction BNP after exercise was 285.2 vs. 37.5 pg/mL in patients with normal diastolic function, and the increase in BNP during exercise was 96.9 vs. 12.4 pg/mL, respectively. Duration of exercise and exercise tolerance in patients with normal diastolic function was better in comparison with the studied patients with disturbed diastolic function, but did not reach statistical significance.. The BNP initial concentration and its value immediately after exercise were significantly higher in subjects with severe diastolic disorders than those in subjects with normal LV diastolic function and in subjects with impaired LV relaxation.

Topics: Aged; Diabetes Mellitus, Type 2; Exercise Test; Humans; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Ventricular Dysfunction, Left

Natriuretic peptide (NP) has been shown to be an effective screening tool to identify patients with Stage B heart failure and to have clinical value in preventing heart failure progression. The impact of associated metabolic confounders on the screening utility of NP needs clarification.. To assess the impact of diabetes mellitus (DM) on NP screening for asymptomatic Stage B heart failure.. The study population consisted of 1368 asymptomatic patients with cardiovascular risk factors recruited from general practice as part of the STOP-HF trial. B-type NP (BNP) was quantified at point-of-care.. BNP was found to be as accurate for detecting Stage B heart failure in DM patients compared to non-DM patients (AUC 0.75 [0.71,0.78] and 0.77 [0.72,0.82], respectively). However, different BNP thresholds are required to achieve the same level of diagnostic sensitivity in DM compared with non-DM patients. To achieve 80% sensitivity a difference of 5-ng/L lower is required for patients with DM.. Although a significantly different BNP threshold is detected for patients with DM, the BNP concentration difference is small and unlikely to warrant a clinically different diagnostic threshold.

Topics: Aged; Biomarkers; Case-Control Studies; Diabetes Mellitus, Type 2; Female; Heart Failure; Humans; Male; Mass Screening; Middle Aged; Natriuretic Peptide, Brain; Risk Factors; ROC Curve; Severity of Illness Index

1. Evaluation of the impact of physical exercise on the secretion of type B natriuretic peptide (BNP) in patients with preserved left ventricular function, in the group after myocardial infarction and in the group with diabetes. 2. Evaluation of the effect of hemodynamic parameters and exercise tolerance on BNP secretion in the study groups. 3. Comparison of echocardiographic image, biochemical changes and exercise tolerance in both groups.. The study included patients with type 2 diabetes without a history of myocardial infarction and patients after myocardial infarction treated with primary angioplasty, with preserved left ventricular systolic function (LV EF ≥ 40%). The study included 99 patients, aged 40-75. Patients had an echocardiographic test performed for systolic and diastolic left ventricle function evaluation, an electrocardiographic exercise test and blood collection for BNP determination before and immediately after the exercise test.. The increase of BNP release after exercise was observed in both groups: in the group with a history of myocardial infarction, the BNP increase was 37.8 ± 45.9 pg/ml, whereas in the group with diabetes 18.1 ± 26.8 pg/ml. BNP after exercise and increase in BNP during exercise was significantly higher in subjects with a history of myocardial infarction (p = 0.008). There was no association between exercise-induced increase in BNP and the duration of exercise or exercise tolerance. Exercise tolerance was higher in subjects with a history of myocardial infarction, but the difference did not reach a statistical significance (METS 8.7 ± 3.3 vs 7.92 ± 2.3; p = 0.08).. 1. During the exercise test an increase in BNP secretion was observed in subjects with diabetes and with the history of myocardial infarction, with preserved LV systolic function. 2. BNP growth during exercise test was significantly higher in patients after myocardial infarction. 3. The exercise-induced BNP growth did not significantly correlate with exercise duration or exercise tolerance measured with the metabolic equivalent - METS.

Topics: Adult; Aged; Diabetes Mellitus, Type 2; Exercise; Exercise Tolerance; Female; Humans; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Ventricular Function, Left

Based on previous experiences, the Food and Drug Administration and the European Medicines Agency recommend that clinical trials for novel antidiabetic drugs are powered to detect increased cardiovascular risk. In this context, data concerning licensed drugs such as metformin and sulfonylureas are conflicting. The influence of baseline cardiovascular risk on any treatment effect appears obvious but has not been formally proven. We therefore evaluated association of metformin and sulfonylureas with cardiovascular events in patients with different cardiovascular risk profiles indicated by N-terminal of the prohormone brain natriuretic peptide (NT-proBNP) levels.. 2024 patients with diabetes mellitus were included in this observational study. The primary endpoint was defined as a combination of cardiovascular events and death. Association of metformin and sulfonylureas was assessed using Cox regression models. Possible differences of these associations in patients with different NT-proBNP levels were studied by stratifying and through interaction analysis.. During a median follow-up of 60 months, the primary endpoint occurred in 522 (26%) of patients. The median age was 63 years. A Cox regression analysis was adjusted for site of treatment, concomitant medication, age, gender, body mass index, glycated haemoglobin, duration of diabetes, glomerular filtration rate, cholesterol, and history of smoking and cardiac disease. Metformin was associated with a decreased risk in the cohort with elevated NT-proBNP ≥300 pg/mL (HR 0.70, p=0.014) and a similar association was found for the interaction between metformin and NT-proBNP (p=0.001). There was neither an association for sulfonylureas nor a significant interaction between sulfonylureas and NT-proBNP.. Metformin is associated with beneficial cardiovascular outcomes in patients with diabetes only when (sub)clinical cardiovascular risk defined by NT-proBNP levels is present.

Topics: Aged; Austria; Biomarkers; Cardiovascular Diseases; Chi-Square Distribution; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Male; Metformin; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Proportional Hazards Models; Prospective Studies; Protective Factors; Risk Assessment; Risk Factors; Sulfonylurea Compounds; Time Factors; Treatment Outcome

We evaluated the ability of 23 novel biomarkers representing several pathophysiological pathways to improve the prediction of cardiovascular event (CVE) risk in patients with type 2 diabetes mellitus beyond traditional risk factors.. We used data from 1002 patients with type 2 diabetes mellitus from the Second Manifestations of ARTertial disease (SMART) study and 288 patients from the European Prospective Investigation into Cancer and Nutrition-NL (EPIC-NL). The associations of 23 biomarkers (adiponectin, C-reactive protein, epidermal-type fatty acid binding protein, heart-type fatty acid binding protein, basic fibroblast growth factor, soluble FMS-like tyrosine kinase-1, soluble intercellular adhesion molecule-1 and -3, matrix metalloproteinase [MMP]-1, MMP-3, MMP-9, N-terminal prohormone of B-type natriuretic peptide, osteopontin, osteonectin, osteocalcin, placental growth factor, serum amyloid A, E-selectin, P-selectin, tissue inhibitor of MMP-1, thrombomodulin, soluble vascular cell adhesion molecule-1, and vascular endothelial growth factor) with CVE risk were evaluated by using Cox proportional hazards analysis adjusting for traditional risk factors. The incremental predictive performance was assessed with use of the c-statistic and net reclassification index (NRI; continuous and based on 10-year risk strata 0-10%, 10-20%, 20-30%, >30%). A multimarker model was constructed comprising those biomarkers that improved predictive performance in both cohorts. N-terminal prohormone of B-type natriuretic peptide, osteopontin, and MMP-3 were the only biomarkers significantly associated with an increased risk of CVE and improved predictive performance in both cohorts. In SMART, the combination of these biomarkers increased the c-statistic with 0.03 (95% CI 0.01-0.05), and the continuous NRI was 0.37 (95% CI 0.21-0.52). In EPIC-NL, the multimarker model increased the c-statistic with 0.03 (95% CI 0.00-0.03), and the continuous NRI was 0.44 (95% CI 0.23-0.66). Based on risk strata, the NRI was 0.12 (95% CI 0.03-0.21) in SMART and 0.07 (95% CI -0.04-0.17) in EPIC-NL.. Of the 23 evaluated biomarkers from different pathophysiological pathways, N-terminal prohormone of B-type natriuretic peptide, osteopontin, MMP-3, and their combination improved CVE risk prediction in 2 separate cohorts of patients with type 2 diabetes mellitus beyond traditional risk factors. However, the number of patients reclassified to a different risk stratum was limited.

Topics: Adult; Biomarkers; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Humans; Male; Matrix Metalloproteinase 3; Middle Aged; Natriuretic Peptide, Brain; Netherlands; Osteopontin; Peptide Fragments; Prospective Studies; Risk Assessment

Soluble fms-like tyrosine kinase-1 (sFlt-1) is an endogenous inhibitor of endothelial growth factors, such as placental growth factor (PlGF), which modulates cardiovascular (CV) remodeling. We determine sFlt-1 levels in patients with heart failure (HF) and its relationship to adverse cardiovascular (CV) events and biomarkers of cardiovascular risk. Levels of sFlt-1 and PlGF levels were also determined in healthy volunteers and patients with type 2 diabetes mellitus (T2DM). SFlt-1 and PlGF were clearly increased in HF patients in comparison to T2DM patients or healthy subjects (p < 0.01). Concentration of sFlt-1 was related to HF severity (p < 0.001) and was correlated to NT-proBNP (ρ = 0.37, p < 0.01), soluble ST2 (ρ = 0.52, p < 0.01), Galectin-3 (ρ = 0.38, p < 0.01), aldosterone (ρ = 0.25, p = 0.01) and PTH(1-84) (ρ = 0.38, p < 0.01). Furthermore, sFlt-1 levels were associated to long-term CV risk. These results suggest a potential role of sFlt-1 in HF and its potential role as biomarker of CV risk.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Diabetes Mellitus, Type 2; Female; Healthy Volunteers; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Placenta Growth Factor; Severity of Illness Index; Vascular Endothelial Growth Factor Receptor-1

Whether biomarkers associated with cardiovascular disease risk also predict incident diabetes mellitus (DM) is unknown. Our objective was to determine if a panel of 18 biomarkers previously associated with risk of cardiovascular disease also predicts incident DM in statin-treated patients with coronary artery disease (CAD). The Treating to New Targets (TNT) study is a randomized trial that compared the efficacy of high (80 mg) versus low (10 mg) dose atorvastatin for the secondary prevention of coronary heart disease events. Fasting plasma levels of standard lipids and of 18 emerging CAD risk biomarkers were obtained after an 8-week run-in period on atorvastatin 10 mg in a random sample of 1,424 TNT patients. After exclusion of patients with DM at baseline (n = 253), 101 patients developed DM during the median follow-up of 4.9 years. Patients with incident DM had lower levels of total and high-molecular weight adiponectin, lipoprotein-associated phospholipase A2 (Lp-PLA2), soluble receptor of advanced glycation end products, and vitamin D compared with patients without incident DM. In contrast, insulin, soluble CD40 ligand, and soluble intercellular adhesion molecule-1 levels were higher in patients with incident DM compared with those without. Plasma levels of C-reactive protein, cystatin C, lipoprotein(a), monocyte chemotactic protein-1, matrix metalloproteinase-9, myeloperoxidase, neopterin, N-terminal fragment of pro-B-type natriuretic peptide, osteopontin, and soluble vascular cell adhesion molecule-1 were comparable in patients with and without incident DM. After multivariate adjustment, total and high-molecular weight adiponectin as well as Lp-PLA2 were negatively associated with incident DM. Results of this study suggest that plasma lipids and some emerging CAD risk biomarkers, such as adiponectin and Lp-PLA2, may be useful for predicting incident DM in statin-treated patients with stable CAD.

Topics: 1-Alkyl-2-acetylglycerophosphocholine Esterase; Adiponectin; Aged; Atorvastatin; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; CD40 Ligand; Chemokine CCL2; Coronary Artery Disease; Cystatin C; Diabetes Mellitus, Type 2; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Incidence; Insulin; Intercellular Adhesion Molecule-1; Lipoprotein(a); Male; Matrix Metalloproteinase 9; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Neopterin; Osteopontin; Peptide Fragments; Peroxidase; Randomized Controlled Trials as Topic; Receptor for Advanced Glycation End Products; Risk Factors; Secondary Prevention; Vascular Cell Adhesion Molecule-1; Vitamin D

We hypothesised that biomarkers representing different pathophysiological pathways of atherosclerosis namely growth differentiation factor 15 (GDF-15), N-terminal pro B-type natriuretic peptide (NT-proBNP) and high-sensitive troponin T (hs-TnT) could enhance cardiovascular risk prediction in patients with type 2 diabetes mellitus.. This is a prospective study in 746 patients with type 2 diabetes mellitus, who were followed up for 60 months. The primary endpoint was defined as unplanned hospitalisation for cardiovascular disease or death. The prognostic performance of the biomarkers of interest (GDF-15 in comparison with NT-proBNP and hs-TnT) was evaluated in univariate as well as in stepwise Cox regression models. HRs are presented per standard unit increase.. The primary endpoint was registered in 171 patients (22.9%). In univariate Cox regression models, GDF-15 as well as hs-TnT provided significant prognostic information. Even after adjusting for established cardiovascular risk factors, GDF-15, hs-TnT and NT-proBNP remained strong independent predictors of the endpoint (logGDF-15: HR 1.37, p<0.01, CI 1.12 to 1.68; loghs-TnT: HR 1.43, p<0.01, CI 1.13 to 1.1.82; logNT-proBNP: HR 1.45, p<0.01, CI 1.26 to 1.66). The number of elevated markers showed a strong complementarity to predict future long-term risk. Adding hs-TnT and GDF-15 to a zero model already including NT-proBNP led to a net reclassification improvement (NRI) of 33.6% (CI 16.0% to 50.8%, NRI for patients with event: 11.1% CI -4.7% to 26.6%, for patients without event: 22.5% CI 13.6% to 30.5%).. GDF-15 and hs-TnT are strong independent cardiovascular biomarkers augmenting the predictive value of NT-proBNP in patients with diabetes.

Topics: Adult; Aged; Austria; Biomarkers; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Disease Progression; Female; Growth Differentiation Factor 15; Hospitalization; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prevalence; Prognosis; Proportional Hazards Models; Prospective Studies; Registries; Risk Assessment; Risk Factors; Time Factors; Troponin T; Up-Regulation

The Goto-Kakizaki (GK) rat, a non-obese model of type 2 diabetes mellitus (T2DM), was generated by the selective inbreeding of glucose-intolerant Wistar rats. This is a convenient model for studying diabetes-induced cardiomyopathy independently from the effects of the metabolic syndrome. We investigated the myocardial functional and structural changes and underlying molecular pathomechanisms of short-term and mild T2DM. The presence of DM was confirmed by an impaired oral glucose tolerance in the GK rats compared with the age-matched nondiabetic Wistar rats. Data from cardiac catheterization showed that in GK rats, although the systolic indexes were not altered, the diastolic stiffness was increased compared with nondiabetics (end-diastolic-pressure-volume-relationship: 0.12 ± 0.04 vs. 0.05 ± 0.01 mmHg/μl, P < 0.05). Additionally, DM was associated with left-ventricular hypertrophy and histological evidence of increased myocardial fibrosis. The plasma pro-B-type natriuretic peptide, the cardiac troponin-T, glucose, and the urinary glucose concentrations were significantly higher in GK rats. Among the 125 genes surveyed using PCR arrays, DM significantly altered the expression of five genes [upregulation of natriuretic peptide precursor-A and connective tissue growth factor, downregulation of c-reactive protein, interleukin-1β, and tumor necrosis factor (TNF)-α mRNA-level]. Of the altered genes, which were evaluated by Western blot, only TNF-α protein expression was significantly decreased. The ECG recordings revealed no significant differences. In conclusion, while systolic dysfunction, myocardial inflammation, and abnormal electrical conduction remain absent, short-term and mild T2DM induce the alteration of cardiac TNF-α at both the mRNA and protein levels. Further assessments are required to reveal if TNF-α plays a role in the early stage of diabetic cardiomyopathy development.

Topics: Animals; Apoptosis; Atrial Natriuretic Factor; Blood Glucose; C-Reactive Protein; Connective Tissue Growth Factor; Diabetes Mellitus, Type 2; Down-Regulation; Echocardiography; Electrocardiography; Fibrosis; Glucose Tolerance Test; Glycosuria; Hypertrophy, Left Ventricular; Immunohistochemistry; In Situ Nick-End Labeling; Inflammation; Interleukin-1beta; Male; Myocardium; Natriuretic Peptide, Brain; Oxidative Stress; Peptide Fragments; Polymerase Chain Reaction; Rats; Rats, Wistar; RNA, Messenger; Signal Transduction; Troponin T; Tumor Necrosis Factor-alpha; Tyrosine; Up-Regulation; Ventricular Dysfunction, Left; Ventricular Function, Left; Ventricular Pressure

Urinary liver-type fatty acid-binding protein (L-FABP) reflects the degree of stress in proximal tubules of the kidney. We examined the level of L-FABP in type-2 diabetes mellitus (T2DM) patients with chronic kidney disease (CKD) stage G1 and G2, and its relationship with cardiac markers and electrocardiographic (ECG) abnormalities. T2DM patients whose estimated glomerular filtration rate (eGFR) was ≥60 mL/min/1.73 m(2) were recruited [n = 276 (165 males), mean age 64 years]. The median level of urinary L-FABP was 6.6 μg/gCr. Urinary L-FABP showed significant correlation with urinary albumin-to-creatinine ratio (ACR) (r = 0.51, p < 0.0001). Median (25th-75th percentile) eGFR was 82 (72-95) mL/min/1.73 m2. We divided patients into four subgroups (group 1, L-FABP ≤8.4 μg/gCr and ACR ≤30 mg/gCr; group 2, L-FABP ≤8.4 μg/gCr and ACR >30 mg/gCr; group 3, L-FABP >8.4 μg/gCr and ACR ≤30 mg/gCr; group 4, L-FABP >8.4 μg/gCr and ACR >30 mg/gCr). Compared with group 1, group 4 was significantly higher in systolic blood pressure, and eGFR using standardized serum cystatin C, high-sensitivity troponin T, and N-terminal pro-brain natriuretic peptide (NT-proBNP). Group 4 had significantly higher level of NT-proBNP than group 3. Groups 2, 3 and 4 showed more ECG abnormalities than group 1. These findings suggest that simultaneous measurement of urinary L-FABP and ACR should be useful to assess cardiovascular damage reflecting on the elevation of cardiac markers and ECG abnormalities in T2DM with CKD G1 and G2.

Topics: Aged; Albuminuria; Arrhythmias, Cardiac; Biomarkers; Creatinine; Cystatin C; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Electrocardiography; Fatty Acid-Binding Proteins; Female; Glomerular Filtration Rate; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Renal Insufficiency, Chronic; Risk Factors; Troponin T

We aimed to evaluate the impact of glycometabolic imbalance as assessed by glycosylated haemoglobin [HbA(1c)] on neurohormonal activation and outcome in chronic heart failure (CHF).. Nine hundred and twenty CHF patients (65 ± 12 years, left ventricular ejection fraction 33 ± 10%, 29% diabetic patients) underwent a thorough humoral and clinical characterization, including HbA(1c), and were then followed up for the endpoint of cardiac death. In the whole population, diagnosis of diabetes resulted in no difference in neurohormonal or echocardiographic data, or in outcome. Conversely, the diabetic patients with HbA(1c) above 7% showed, in comparison to both diabetic patients with HbA(1c) below 7% and non-diabetic individuals, higher plasma renin activity (1.81, 0.48-5.68 vs. 1.23, 0.43-2.8 and 1.29, 0.44-5 ng/ml/h, respectively; P < 0.01 for both), N-terminal pro-brain natriuretic peptide (NT-pro-BNP) (1602, 826-3498 vs. 1022, 500-3543 and 1134, 455-3545 ng/l, respectively; P < 0.01 for both) and worse symptoms with a higher rate of cardiac mortality vs. both diabetic patients with HbA1(c) below 7% and non-diabetic individuals (P < 0.05 for both). In the left ventricular ejection fraction 38-50% tertile (mild left ventricular dysfunction), elevated HbA(1c) was associated with higher NT-pro-BNP and PRA (P < 0.01), and, alongside NT-pro-BNP, resulted the only independent predictor of outcome beyond diagnosis of diabetes. HbA(1c) failed to show up differences in neuroendocrine activation or in outcome in moderate and severe left ventricular dysfunction tertiles.. Glycometabolic imbalance, as represented by HbA(1c), is associated with neurohormonal activation and poor prognosis in CHF patients, beyond diabetes. The impact of metabolic derangement on prognosis appears greater at the early stages of CHF, when it might exacerbate neurohormonal activation.

Topics: Aged; Biomarkers; Chronic Disease; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Glycated Hemoglobin; Heart Failure; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Prospective Studies; Renin; Ventricular Dysfunction, Left

In spite of accumulating evidences suggesting an inverse association between insulin resistance and plasma B-type natriuretic peptide (BNP) levels, the effect of daily physical activity on plasma BNP in individuals with glucose intolerance remains unknown. We investigated the association of physical activity level (PAL) with plasma BNP in patients with impaired fasting glucose, impaired glucose tolerance and type 2 diabetes.. Cross-sectional study.. Outpatients visiting the National Center for Global Health and Medicine Kohnodai Hospital.. A total of 60 patients with glucose intolerance who did not take any hypoglycaemic agents, cholesterol-lowering agents and antihypertensive agents were recruited. Patients who were diagnosed as having heart failure and renal impairment, engaged in sports-like exercise and resistance training were excluded.. PAL was objectively measured by a triaxial accelerometer. The association between PAL and plasma BNP levels was assessed by multiple regression analysis.. PAL was positively correlated with plasma BNP levels (r=0.296, p=0.021). PAL was still significantly correlated with plasma BNP levels after adjustment for age (β=0.290, p=0.014), and adjustment for age and body mass index (β=0.282, p=0.018). Plasma BNP levels were inversely correlated with serum insulin levels (r=-0.350, p=0.006) and homeostasis model assessment-estimated insulin resistance (HOMA-IR; r=-0.363, p=0.004). Serum insulin levels (mean±SD, 8.1±6.4 μU/mL) and HOMA-IR (2.4±1.9) in the high-BNP group were significantly lower than those (11.2±7.4 μU/mL and 3.7±3.0, respectively) in the low-BNP group.. Our findings propose the possibility that plasma BNP may be increased by daily physical activity and BNP is associated with insulin resistance.

Topics: Adult; Aged; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Exercise; Female; Glucose Intolerance; Humans; Insulin; Male; Middle Aged; Natriuretic Peptide, Brain; Time Factors

We selected the most informative protein biomarkers for the prediction of incident cardiovascular disease (CVD) in people with type 2 diabetes.. In this nested case-control study we measured 42 candidate CVD biomarkers in 1,123 incident CVD cases and 1,187 controls with type 2 diabetes selected from five European centres. Combinations of biomarkers were selected using cross-validated logistic regression models. Model prediction was assessed using the area under the receiver operating characteristic curve (AUROC).. Sixteen biomarkers showed univariate associations with incident CVD. The most predictive subset selected by forward selection methods contained six biomarkers: N-terminal pro-B-type natriuretic peptide (OR 1.69 per 1 SD, 95% CI 1.47, 1.95), high-sensitivity troponin T (OR 1.29, 95% CI 1.11, 1.51), IL-6 (OR 1.13, 95% CI 1.02, 1.25), IL-15 (OR 1.15, 95% CI 1.01, 1.31), apolipoprotein C-III (OR 0.79, 95% CI 0.70, 0.88) and soluble receptor for AGE (OR 0.84, 95% CI 0.76, 0.94). The prediction of CVD beyond clinical covariates improved from an AUROC of 0.66 to 0.72 (AUROC for Framingham Risk Score covariates 0.59). In addition to the biomarkers, the most important clinical covariates for improving prediction beyond the Framingham covariates were estimated GFR, insulin therapy and HbA1c.. We identified six protein biomarkers that in combination with clinical covariates improved the prediction of our model beyond the Framingham Score covariates. Biomarkers can contribute to improved prediction of CVD in diabetes but clinical data including measures of renal function and diabetes-specific factors not included in the Framingham Risk Score are also needed.

Topics: Aged; Apolipoprotein C-III; Area Under Curve; Biomarkers; Cardiovascular Diseases; Case-Control Studies; Diabetes Complications; Diabetes Mellitus, Type 2; Europe; Female; Glomerular Filtration Rate; Glycated Hemoglobin; Humans; Insulin; Interleukin-15; Interleukin-6; Logistic Models; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Risk Factors; ROC Curve; Troponin T

Blood flow in lower extremity arteries is frequently impaired in diabetic patients even though they have a normal ankle-brachial index (ABI 1.0-1.4). Risk factors contributing to this lower extremity arterial disease have not been fully elucidated. We enrolled 52 type 2 diabetic patients with normal ABI and 30 age-matched nondiabetic subjects consecutively admitted to our hospital. Plasma B-type natriuretic peptide (BNP) concentrations were measured. Distensibility in ascending thoracic and abdominal aortas as well as total flow volume and resistive index at popliteal artery were evaluated by gated magnetic resonance imaging. An automatic device was used to measure ABI and brachial-ankle pulse-wave velocity (baPWV). Diabetic patients showed lower distensibility in ascending thoracic aorta (p<0.001) and total flow volume (p<0.001) and higher baPWV (p<0.001) and resistive index (p=0.005) and similar BNP and distensibility in abdominal aorta compared to nondiabetic subjects. Simple linear regression analyses revealed that distensibility in ascending thoracic (p=0.019) and abdominal (p=0.030) aortas positively as well as baPWV (p=0.020), resistive index (p<0.001) and BNP (p<0.001) negatively correlated with total flow volume. Stepwise multiple regression analysis demonstrated that increased BNP and resistive index were independent risk factors for total flow volume in diabetic patients (r(2)=0.639, p<0.001). These results indicate that increased plasma BNP levels and peripheral vascular resistance, but not decreased aortic distensibility, associate with impaired blood flow in lower extremity arteries in diabetic patients.

Topics: Aged; Ankle Brachial Index; Aorta; Aortography; Biomarkers; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Elasticity; Female; Humans; Japan; Magnetic Resonance Angiography; Male; Middle Aged; Natriuretic Peptide, Brain; Peripheral Arterial Disease; Popliteal Artery; Pulse Wave Analysis; Regional Blood Flow; Risk Factors; Up-Regulation; Vascular Resistance

In European populations, the NPPB rs198389 single nucleotide polymorphism (SNP) is associated with a reduced risk of type 2 diabetes mellitus (T2DM). We investigated the putative associations between NPPB rs198389, the T2DM risk and quantitative metabolic traits in an Algerian population.. The association analysis was performed as a T2DM case-control study (with 78 cases and 645 controls) nested into the ISOR population-based study.. The NPPB rs198389 SNP was not associated with T2DM (odds ratio (OR) [95% confidence interval (CI)]=0.73 [0.51-1.04], p=0.08). However, the C allele was associated with lower fasting plasma insulin levels (p=0.05) and a lower homeostatic model assessment insulin resistance index (p=0.05) in non-diabetic individuals.. The NPPB rs198389 SNP might modulate fasting insulin levels in an Algerian population.

Topics: Adult; Algeria; Case-Control Studies; Diabetes Mellitus, Type 2; Female; Gene Frequency; Genetic Association Studies; Genetic Predisposition to Disease; Humans; Insulin; Insulin Resistance; Male; Middle Aged; Natriuretic Peptide, Brain; Phenotype; Polymorphism, Single Nucleotide; Risk

Emerging evidence suggests female type 2 diabetes (T2DM) patients may fare worse than males with respect to cardiovascular complications. Hence the impact of sex on relative progression of left ventricular (LV) remodeling in obese db/db mice was characterized.. The changes in parameters of LV hypertrophy (heart weight, pro-hypertrophic gene expression, cardiomyocyte size) and fibrosis (LV collagen deposition and oxidative stress), in parallel with body weight and blood glucose and lipid profiles, in male and female db/db T2DM mice, at 10, 14, and 18 weeks of age, were determined.. Diabesity-induced cardiac remodeling was at least comparable in female (compared to male) mice. Females exhibited enhanced systemic oxidative stress and nonesterified fatty acid levels. Progression of LV pro-hypertrophic (β-myosin heavy chain, B-type natriuretic peptide) and pro-oxidant gene expression (NADPH oxidase subunit Nox2, plasminogen activator inhibitor-1 PAI-I) was, however, exaggerated in females when expressed relative to 10-week-old db/db mice. Increased cardiomyocyte width was also evident earlier in db/db females than males. No other gender differences were observed.. Progressive, age-dependent development of cardiac remodeling in db/db mice parallels impairments in glucose handling and oxidative stress. Certain aspects of the T2DM-induced LV remodeling response may have an earlier and/or exaggerated onset in diabetic females.

Topics: Animals; Blood Glucose; Diabetes Mellitus, Type 2; Female; Fibrosis; Heart; Hypertrophy, Left Ventricular; Male; Mice; Mice, Obese; Models, Animal; Myocytes, Cardiac; Natriuretic Peptide, Brain; Oxidative Stress; Plasminogen Activator Inhibitor 1; Reactive Oxygen Species; Sex Factors; Ventricular Remodeling

In patients with type 2 diabetes, cardiovascular disease (CVD) is the major cause of morbidity and mortality. We evaluated the combination of NT-proBNP and coronary artery calcium score (CAC) for prediction of combined fatal and non-fatal CVD and mortality in patients with type 2 diabetes and microalbuminuria (>30 mg/24-h), but without known coronary artery disease. Moreover, we assessed the predictive value of a predefined categorisation of patients into a high- and low-risk group at baseline.. Prospective study including 200 patients. All received intensive multifactorial treatment. Patients with baseline NT-proBNP > 45.2 ng/L and/or CAC ≥ 400 were stratified as high-risk patients (n = 133). Occurrence of fatal- and nonfatal CVD (n = 40) and mortality (n = 26), was traced after 6.1 years (median).. High-risk patients had a higher risk of the composite CVD endpoint (adjusted hazard ratio [HR] 10.6 (95 % confidence interval [CI] 2.4-46.3); p = 0.002) and mortality (adjusted HR 5.3 (95 % CI 1.2-24.0); p = 0.032) compared to low-risk patients. In adjusted continuous analysis, both higher NT-proBNP and CAC were strong predictors of the composite CVD endpoint and mortality (p ≤ 0.0001). In fully adjusted models mutually including NT-proBNP and CAC, both risk factors remained associated with risk of CVD and mortality (p ≤ 0.022). There was no interaction between NT-proBNP and CAC for the examined endpoints (p ≥ 0.31).. In patients with type 2 diabetes and microalbuminuria but without known coronary artery disease, NT-proBNP and CAC were strongly associated with fatal and nonfatal CVD, as well as with mortality. Their additive prognostic capability holds promise for identification of patients at high risk.

Topics: Aged; Albuminuria; Asymptomatic Diseases; Biomarkers; Cardiovascular Diseases; Cohort Studies; Coronary Artery Disease; Diabetes Mellitus, Type 2; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Multidetector Computed Tomography; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Proportional Hazards Models; Prospective Studies; Vascular Calcification

This study looked at whether the inverse association of circulating N-terminal pro-B-type natriuretic peptide (NT-proBNP) with incident diabetes is modified by changes in NT-proBNP (ΔNT-proBNP) levels.. Plasma NT-proBNP was assayed at baseline and 3.2 years later (visit 3) in the Multi-Ethnic Study of Atherosclerosis (MESA). ΔNT-proBNP was calculated as NT-proBNP visit3-NT-proBNP baseline. A Poisson distribution was fitted to determine the incidence density of diabetes, adjusted for age, race, gender, educational attainment, antihypertensive medication, total intentional exercise and plasma IL-6 levels. In the primary analysis (n=3236 without diabetes up to visit 3, followed for a mean of 6.3 years), incidence density was regressed for the following categories of baseline NT-proBNP: (1)<54.4 pg/mL; (2) 54.4-85.9 pg/mL; and (3) 86-54.2 pg/mL. This was crossed with categories of ΔNT-proBNP as medians (ranges): (1) -6.2 (-131-11.7) pg/mL; (2) 19.8 (11.8-30.1) pg/mL; (3) 44.0 (30.2-67.9) pg/mL; and (4) 111.2 (68.0-3749.9) pg/mL.. The incidence density of diabetes followed a U-shaped association across categories of ΔNT-proBNP within categories of baseline NT-proBNP after adjusting for other covariates (P=0.02). At each level of baseline NT-proBNP, the incidence density of diabetes was lowest for small-to-moderate increases in NT-proBNP.. This analysis suggests that NT-proBNP has a biphasic association with diabetes in which the risk of incident diabetes decreases within a 'physiological range' of ΔNT-proBNP, and plateaus or increases as NT-proBNP concentrations increase, probably in response to pathophysiological conditions leading to high levels of NT-proBNP.

Topics: Aged; Aged, 80 and over; Asymptomatic Diseases; Atherosclerosis; Cohort Studies; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Humans; Incidence; Interleukin-6; Male; Middle Aged; Minnesota; Natriuretic Peptide, Brain; Peptide Fragments; Poisson Distribution; Risk; Up-Regulation

Type 2 diabetes (DMT2) combined with ischemic heart disease (IHD) promotes the occurrence and development of coronary atherosclerosis. We aimed to provide a theoretical basis for improving patient prognosis through analyzing expression of plasma brain natriuretic peptide (BNP), endothelin-1 (ET 1), and matrix metalloproteinase 9 (MMP-9).. Enzyme-linked immunosorbent assay (ELISA) was used to detect BNP, ET-1, and MMP-9 levels in 50 patients with DMT2 only (group A), 47 patients with IHD only (group B), 43 patients with comorbid (both) IHD and DMT2 (group C), and 50 health controls (group D). Group C was further divided into single-branch lesion group, double-branch lesions group, and triple-branch lesion group according to coronary angiography, or cardiac function grade II, III, and IV group according to cardiac function, and their BNP, ET-1, and MMP-9 levels were compared.. Compared with group D, TG, diastolic, and systolic blood pressure were all significantly elevated in groups A, B, and C. Group C exhibited obviously higher glycosylated hemoglobin than group A. Gensini score in group C was markedly higher than in group B. Compared with group D, BNP, ET-1, and MMP-9 levels were all increased in groups A, B, and C. Group C showed higher levels of BNP, ET-1, and MMP-9 than group A and B. BNP, ET-1, and MMP-9 levels in the triple-branch lesions group were higher than in the single-branch lesions group and double-branch lesions group. The cardiac function grade IV group presented higher levels of BNP, ET-1, and MMP-9 than did the grade II and III groups. BNP, ET-1, and MMP-9 showed a positive correlation to each other.. BNP, ET-1, and MMP-9 may participate in the occurrence and development of comorbid DMT2 and IHD. They are important objective indicators for evaluating severity and prognosis of patients with comorbid DMA2 and IHD.

Topics: Adult; Aged; Biomarkers; Coronary Artery Disease; Diabetes Mellitus, Type 2; Endothelin-1; Enzyme-Linked Immunosorbent Assay; Female; Heart Function Tests; Humans; Male; Matrix Metalloproteinase 9; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Prognosis

Cardiac-specific troponin detected with the new high-sensitivity assays can be chronically elevated in response to cardiovascular comorbidities and confer important prognostic information, in the absence of unstable coronary syndromes. Both diabetes mellitus and coronary artery disease are known predictors of troponin elevation. It is not known whether diabetic patients with coronary artery disease have different levels of troponin compared with diabetic patients with normal coronary arteries. To investigate this question, we determined the concentrations of a level 1 troponin assay in two groups of diabetic patients: those with multivessel coronary artery disease and those with angiographically normal coronary arteries.. We studied 95 diabetic patients and compared troponin in serum samples from 50 patients with coronary artery disease (mean age = 63.7, 58 % male) with 45 controls with angiographically normal coronary arteries. Brain natriuretic peptide and the oxidative stress biomarkers myeloperoxidase, nitrotyrosine and oxidized LDL were also determined.. Diabetic patients with coronary artery disease had higher levels of troponin than did controls (median values, 12.0 pg/mL (95 % CI:10-16) vs 7.0 pg/mL (95 % CI: 5.9-8.5), respectively; p = 0.0001). The area under the ROC curve for the diagnosis of CAD was 0.712 with a sensitivity of 70 % and a specificity of 66 %. Plasma BNP levels and oxidative stress variables (myeloperoxidase, nitrotyrosine, and oxidized LDL) were not different between the two groups. In a multivariate analysis, gender (p = 0.04), serum glucose (0.03) and Troponin I (p = 0.01) had independent statistical significance.. Troponin elevation is related to the presence of chronic coronary artery disease in diabetic patients with multiple associated cardiovascular risk factors. Troponin may serve as a biomarker in this high-risk population.. http://www.controlled-trials.com. ISRCTN26970041.

Topics: Aged; Biomarkers; Case-Control Studies; Cholesterol, LDL; Coronary Artery Disease; Diabetes Mellitus, Type 2; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Oxidation-Reduction; Peroxidase; Risk Factors; Troponin C; Tyrosine

Hyponatremia has been associated with an increased mortality risk in the general population. Diabetes is a condition predisposing for elevated levels of arginine vasopressin (AVP) and heart failure, both common causes of hyponatremia. These factors, however, are also associated with an increased mortality risk. We aimed to investigate whether serum sodium is associated with cardiovascular and all-cause mortality in type 2 diabetes and whether these associations could be explained by copeptin, a surrogate for AVP, or NT-proBNP, a marker for heart failure.. Patients with type 2 diabetes participating in the observational ZODIAC study were included. Cox regression analyses were used to investigate the association of serum sodium with mortality.. We included 1068 patients (age 67 ± 12 years, 45% male, serum sodium 142 ± 3 mmol/L). After 15 years of follow-up, 519 patients (49%) died, with 225 cardiovascular deaths (21%). In univariable analyses, serum sodium, copeptin, and NT-proBNP were all significantly associated with cardiovascular and all-cause mortality. These associations remained significant after combination of these markers in a multivariable model. Serum sodium and NT-proBNP remained significantly associated with mortality after further adjustment for potential confounders, whereas copeptin lost significance after adjustment for SCr and ACR.. Low serum sodium was associated with an increased risk of cardiovascular and all-cause mortality in type 2 diabetes. Moreover, these associations were not explained by copeptin and NT-proBNP. Whether low serum sodium itself leads to poor outcome or is a marker for (unidentified) co-morbidity severity or use of specific medications remains to be elucidated.

Topics: Aged; Aged, 80 and over; Biomarkers; Cardiovascular Diseases; Cause of Death; Diabetes Mellitus, Type 2; Female; Glycopeptides; Humans; Hyponatremia; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Proportional Hazards Models; Risk Factors; Sodium

Elevated preprocedural N-term pro-B-type natriuretic peptide (NT-pro-BNP) and postprocedural cardiac troponin I (cTnI) are related to a poor cardiac outcome in the non-diabetic population. We hypothesized that preprocedural NT-pro-BNP might be a useful marker in predicting periprocedural myocardial injury (PMI) following elective percutaneous coronary intervention (PCI) in type 2 diabetes (T2D).. We prospectively enrolled 1194 consecutive diabetic patients with normal cardiac function and preprocedural cTnI who were successfully undergoing elective PCI. Preprocedural NT-pro-BNP levels were assessed at admission, and PMI was evaluated by analysis of cTnI within 24 hours. The relationship between preprocedural NT-pro-BNP levels and the peak values of cTnI after PCI was examined.. Patients with high baseline NT-pro-BNP levels had higher postprocedural cTnI levels (β = 0.123, p < 0.001). In the multivariable model, NT-pro-BNP was associated with higher risk of postprocedural cTnI elevation above 1 × upper limit of normal (ULN, OR, 3.13; 95% CI, 1.51-6.50; p = 0.002), 3 × ULN (OR, 2.44; 95% CI, 1.17-5.08; p = 0.018), 5 × ULN (OR, 3.18; 95% CI, 1.44-7.0; p = 0.004), respectively. Moreover, the incidence of cTnI elevation was higher in patients with the upper tertile of NT-pro-BNP levels than that in ones with the lower tertile of NT-pro-BNP levels (> 1 × ULN: 63.1% vs. 50.0%, p < 0.001; > 3 × ULN: 39.2% vs. 31.9%, p = 0.032; > 5 × ULN: 30.4% vs. 21.9%, p < 0.006; respectively).. Our data, for the first time, demonstrated that increased preprocedural NT-pro-BNP levels were strongly and independently associated with a higher risk of PMI, suggesting that baseline NT-pro-BNP level might be a useful marker for predicting PMI following PCI in diabetic patients without cardiac dysfunction.

Topics: Aged; Biomarkers; Diabetes Mellitus, Type 2; Humans; Intraoperative Complications; Middle Aged; Multivariate Analysis; Myocardial Infarction; Natriuretic Peptide, Brain; Peptide Fragments; Percutaneous Coronary Intervention; Perioperative Period; Prognosis; Troponin I

The number of patients with type 2 diabetes mellitus (T2DM) is progressively increasing, and diabetic cardiovascular complications have become a public health problem. Brain or B-type natriuretic peptide (BNP) is a cardiac hormone synthesized as a pre-pro-peptide. pro-BNP is produced by cleaving the signal peptide then two proprotein convertases, corin and furin cleave pro-BNP to form a biologically active hormone. Two corin single nucleotide polymorphisms (SNPs) have been reported to alter corin protein conformation and impair its biological activity.. We aimed to investigate the potential role of corin and furin in comparison to BNP as biomarkers for predicting cardiovascular complications in T2DM patients. The association of corin gene SNPs with corin levels was also examined.. Seventy-five subjects were recruited in this study, including 25 T2DM patients with complications, 25 T2DM patients without complications as well as 25 healthy subjects. Plasma BNP, corin and furin levels were measured using enzyme-linked immunosorbent assays. Two corin SNPs were genotyped using allele specific oligonucleotide-polymerase chain reaction.. Both furin and BNP were found to be more sensitive than corin (80% versus 56%, p = 0.008), whereas furin showed higher specificity when compared to BNP (96% versus 84%, p = 0.041) and corin (96% versus 64%, p < 0.0001) in predicting cardiovascular complications in T2DM patients. Corin SNPs are not associated with corin levels, neither in the entire study cohort nor in the subgroup of T2DM patients with cardiovascular complications (p > 0.05).. Furin may be useful, either alone or in combination with other biomarkers, for cardiovascular risk stratification assessment in T2DM patients.

Topics: Aged; Biomarkers; Cardiovascular Diseases; Case-Control Studies; Diabetes Mellitus, Type 2; Female; Furin; Gene Frequency; Genotype; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Polymorphism, Single Nucleotide; Prognosis; ROC Curve; Serine Endopeptidases

The blood concentration of high-sensitivity cardiac troponin T (hs-cTnT) is an established, useful biomarker for evaluating the pathogenesis of heart failure and predicting cardiovascular events. The aim of this study was to evaluate factors that are potentially associated with elevated blood hs-cTnT in patients with type 2 diabetes mellitus.. Patients with type 2 diabetes mellitus (N=280, 111 men and 169 women; mean ± SD age: 71±9 years) with no history of cardiovascular events were enrolled. Relationships between hs-cTnT level and various clinical parameters were examined.. Hs-cTnT was detected in 244 (87.1%) patients. There were no significant relationships between hs-cTnT and fasting blood glucose levels or insulin resistance. hs-cTnT was significantly correlated with advanced glycation end-product levels at the skin (r=0.23, p<0.001), blood concentrations of brain natriuretic peptide (r=0.23, p<0.001), reactive oxygen metabolites as markers of oxidative stress (r=0.28, p<0.001), and the augmentation index at the radial artery as marker of arterial reflection (r=0.31, p<0.001). Furthermore, multiple regression analysis revealed that these factors were also selected as independent variables, with hs-cTnT as a subordinate factor.. These results indicate that novel cardiovascular risk factors including advanced glycation end-products, in vivo oxidative stress, and high arterial reflection are closely associated with high concentrations of blood hs-cTnT in patients with type 2 diabetes mellitus.

Topics: Aged; Aged, 80 and over; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Glycation End Products, Advanced; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Reactive Oxygen Species; Regression Analysis; Risk Factors; Troponin T

Although low dietary salt intake has beneficial effects on BP (blood pressure), low 24hUNa (24 h urinary sodium excretion), the most accurate estimate of dietary salt intake, is associated with increased mortality in people with diabetes. In the non-diabetic population, low salt intake is associated with increased RAAS (renin-angiotensin-aldosterone system) activity. In this cross-sectional study, we examined the relationship between 24hUNa, PRA (plasma renin activity), serum aldosterone and BNP (brain natriuretic peptide) in patients with diabetes. Clinical characteristics, 24hUNa, PRA, serum aldosterone and BNP were recorded in 222 consecutive patients (77% with Type 2 diabetes) attending a diabetes clinic at a tertiary hospital. The relationship between 24hUNa, serum aldosterone, PRA, BNP, urinary potassium excretion, serum potassium, serum sodium, eGFR (estimated glomerular filtration rate), urinary albumin excretion and HbA1c (glycated haemoglobin) was examined by a multivariable regression model. Levels of 24hUNa significantly predicted serum aldosterone in a linear fashion (R²=0.20, P=0.002). In the subgroup of patients (n=46) not taking RAAS-modifying agents, this relationship was also observed (R²=0.10, P=0.03), and the effect of 24hUNa on serum aldosterone was found to be more pronounced than in the whole cohort (coefficient=-0.0014, compared with -0.0008). There was no demonstrable relationship between 24hUNa and PRA or BNP. Low 24hUNa is associated with increased serum aldosterone in people with diabetes, in the presence and absence of RAAS-modifying agents. This raises the possibility that stimulation of the RAAS may be a mechanism that contributes to adverse outcomes observed in patients with low 24hUNa.

Topics: Aged; Aldosterone; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Cross-Sectional Studies; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diuretics; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Renin; Renin-Angiotensin System; Sodium

Glycemic control affects cardiovascular risk factors positively. The purpose of this study was to assess B-type natriuretic peptide (BNP) levels in patients with poorly controlled diabetes before and after glycemic regulation was achieved.. The study was performed in a prospective design. The study population consisted of 79 consecutive diabetic patients with poor glycemic control. All subjects underwent transthoracic echocardiography. Levels of fasting plasma glucose, glycosylated hemoglobin (HbA1c), lipid parameters, and BNP were measured before the onset of the treatment and after glycemic regulation was achieved.. A significant decrease in BNP (95.0 [4.0-1807] ng/L vs. 52.0 [2.1-987.0] ng/L, p < 0.001) levels were observed, after improving glycemic control. The decrease in BNP levels was positively correlated with the decrease in HbA1c (r = 0.345, p = 0.003) and fasting plasma glucose (r = 0.366, p = 0.002). There was no correlation between the decrease in BNP levels and lipid parameters (p = NS).. We conclude that poor glycemic control may cause high levels of BNP which may lead to overdiagnosis of congestive heart failure. We suggest that HbA1c and fasting plasma glucose should be checked in patients with high levels of BNP.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Glycated Hemoglobin; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Prospective Studies

OBJECTIVE Current methods of risk stratification in patients with type 2 diabetes are suboptimal. The current study assesses the ability of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) to improve the prediction of cardiovascular events and death in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS A nested case-cohort study was performed in 3,862 patients who participated in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial. RESULTS Seven hundred nine (18%) patients experienced a major cardiovascular event (composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke) and 706 (18%) died during a median of 5 years of follow-up. In Cox regression models, adjusting for all established risk predictors, the hazard ratio for cardiovascular events for NT-proBNP was 1.95 per 1 SD increase (95% CI 1.72, 2.20) and the hazard ratio for hs-cTnT was 1.50 per 1 SD increase (95% CI 1.36, 1.65). The hazard ratios for death were 1.97 (95% CI 1.73, 2.24) and 1.52 (95% CI 1.37, 1.67), respectively. The addition of either marker improved 5-year risk classification for cardiovascular events (net reclassification index in continuous model, 39% for NT-proBNP and 46% for hs-cTnT). Likewise, both markers greatly improved the accuracy with which the 5-year risk of death was predicted. The combination of both markers provided optimal risk discrimination. CONCLUSIONS NT-proBNP and hs-cTnT appear to greatly improve the accuracy with which the risk of cardiovascular events or death can be estimated in patients with type 2 diabetes.

Topics: Aged; Biomarkers; Cardiovascular Diseases; Case-Control Studies; Cohort Studies; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Proportional Hazards Models; Risk Assessment; Troponin T

Liraglutide treatment can improve glycemic control with a concomitant weight loss, but the underlying mechanism on weight loss is not completely understood. Cardiac natriuretic peptides (NPs) can resist body fat accumulation through increasing adipocytes lypolysis. In this study, we tested the hypothesis that liraglutide-induced weight loss was associated with increased plasma NPs concentrations.. Thirty-one outpatients with type 2 diabetes (T2D) treated with metformin and other oral antidiabetic drugs except for thiazolidinediones (TZDs) were subcutaneously administered with liraglutide for 12 weeks. Body composition, abdominal visceral adipose tissue areas (VAT) and subcutaneous adipose tissue areas (SAT) were assessed at pre- and post-treatment by dual-energy X-ray absorptiometry (DXA) scanning and abdominal computerized tomography (CT). Plasma atrial natriuretic peptides (ANP) and B-type ventricular natriuretic peptides (BNP) concentrations were tested by commercial ELISA Kit quantitatively.. Following 12-week liraglutide treatment, body weight, waist circumference, total fat and lean mass, fat percentage, SAT and VAT areas were significantly reduced from baseline. Concurrently, plasma ANP and BNP levels were significantly increased following 12-week liraglutide treatment. There were significant correlations between the reductions in body compositions and the increases in both plasma ANP and BNP levels.. There were significant correlations between increases in both plasma ANP and BNP levels and changes in liraglutide-induced body composition. Our data implied that increases in plasma NPs may add a novel dimension to explain how liraglutide induces weight loss.

Topics: Adult; Atrial Natriuretic Factor; Biomarkers; Body Composition; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Glucagon-Like Peptide 1; Humans; Hypoglycemic Agents; Liraglutide; Male; Middle Aged; Natriuretic Peptide, Brain; Natriuretic Peptides; Obesity; Prospective Studies

Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Diabetes Mellitus, Type 2; Female; Heart Diseases; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments

Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Diabetes Mellitus, Type 2; Female; Heart Diseases; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments

Diabetes is a major risk factor for heart failure (HF). We examined whether baseline HbA1c level predicts HF incidence independent of other HF risk factors, including baseline cardiac structural and functional abnormalities.. In patients with type 2 diabetes, multivariable Cox regression models were constructed to examine the independent association between baseline HbA1c and future HF hospitalization.. In 608 subjects (mean age, 66.5 years; men, 68%; mean HbA1c, 9.1% (76 mmol/mol)), 92 were hospitalized for HF during a median follow-up of 6 years. For a 1% (11 mmol/mol) increase in baseline HbA1c, the hazard ratio for HF was 1.23 (95% confidence interval, 1.1-1.7, p<0.001) with adjustment for age, sex, body mass index, blood pressure and plasma B-type natriuretic peptide (BNP) level. The effect of HbA1c on HF was independent of baseline left ventricular (LV) ejection fraction, the ratio of peak early to late diastolic filling velocity, and prevalent/incident coronary heart disease (CHD), and was more evident in patients with enlarged LV, decreased systolic function, prevalent CHD, or prevalent HF.. In patients with type 2 diabetes, HbA1c significantly predicts future HF hospitalization independent of baseline BNP level or echocardiographic parameters.

Topics: Aged; Biomarkers; Diabetes Mellitus, Type 2; Disease Progression; Female; Follow-Up Studies; Glycated Hemoglobin; Heart Failure; Hospitalization; Humans; Japan; Male; Natriuretic Peptide, Brain; Prevalence; Prognosis; Retrospective Studies; Ventricular Function

Among people with type 2 diabetes the relationship between central obesity and cardiovascular mortality has not been definitely assessed. Moreover, NT-proBNP is negatively associated with central obesity, but no study has examined their combined effect on survival. We have examined these issues in a well-characterized population-based cohort.. Survival data of 2272 diabetic people recruited in 2000 who had no other chronic disease have been updated to 31 December 2006. NT-proBNP was measured in a subgroup of 1690 patients. Cox proportional hazards modeling was employed to estimate the independent associations between cardiovascular and all-cause mortality and waist circumference. Mean age was 67.9 years, 49.3% were men. Both age and NT-proBNP were negatively correlated with waist circumference (r = -0.11, p<0.001 and r = -0.07, p = 0.002). Out of 2272 subjects, 520 deaths (221 for CV mortality) occurred during a median follow-up of 5.4 years. Central obesity was not associated with CV mortality (hazard ratio, HR, adjusted for age, sex, diabetes duration, 1.14, 95% CI 0.86-1.52). NTproBNP was a negative confounder and age a strong modifier of this relationship (p for interaction<0.001): age<70 years, fully adjusted model HR = 3.52 (1.17-10.57) and age ≥70 years, HR = 0.80 (0.46-1.40). Respective HRs for all-cause mortality were 1.86 (1.03-3.32) and 0.73 (0.51-1.04).. In diabetic people aged 70 years and lower, central obesity was independently associated with increased cardiovascular mortality, independently of the negative effect of NT-proBNP. In contrast, no effect on 6-years survival was evident in diabetic people who have yet survived up to 70 years.

Topics: Age Factors; Aged; Aged, 80 and over; Cardiovascular Diseases; Cause of Death; Comorbidity; Diabetes Mellitus, Type 2; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Obesity, Abdominal; Peptide Fragments; Population Surveillance; Prevalence; Risk Factors

Topics: Cardiovascular Diseases; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Troponin T

Topics: Cardiovascular Diseases; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Troponin T

We investigated microvascular event risk in people with type 2 diabetes and assessed whether N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin T (hsTnT) improved prediction.. We performed a case-cohort study, including 439 incident cases of microvascular events (new or worsening nephropathy or retinopathy) and 2,946 noncase subjects identified from participants in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial. NT-proBNP and hsTnT were measured in stored plasma samples using automated commercial assays.. After adjustment for age, sex, and randomized treatment, the hazard ratios for microvascular events per 1-SD increase in the log-transformed hsTnT and NT-proBNP were 1.67 (95% CI 1.51-1.85) and 1.63 (1.44-1.84), respectively. After further adjustment for classical and diabetes-related cardiovascular disease risk factors, the hazard ratios attenuated to 1.40 (1.24-1.58) and 1.41 (1.24-1.60), respectively. While the C statistic did not improve on addition of hsTnT or NT-proBNP for the total microvascular end point, a combination of both markers improved the prediction of nephropathy (P = 0.033) but not retinopathy (P = 0.72). The corresponding net reclassification indices in a three-risk category model (<10%, 10-15%, and >15% 5-year risk) for all microvascular events were 7.31% (95% CI 2.24-12.79) for hsTNT addition, 6.23% (1.74-11.5) for NT-proBNP addition, and 7.1% (1.5-12.9) for both markers together.. These data suggest that cardiac biomarkers moderately improve microvascular event risk prediction, in particular the risk of nephropathy. Further studies examining the value of this approach for trial design and clinical use are warranted.

Topics: Biomarkers; Case-Control Studies; Cohort Studies; Diabetes Mellitus, Type 2; Female; Humans; Incidence; Kidney Diseases; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Risk Assessment; Risk Factors; Troponin

The aim of this study was to investigate the association of N-terminal pro-brain natriuretic peptide (NT-proBNP) with traditional cardiovascular risk factors and incident cardiovascular events in older people with type 2 diabetes.. In the prospective phase of the Edinburgh Type 2 Diabetes Study, 1066 men and women aged 60 to 75 years with type 2 diabetes mellitus were followed for 4 years; 112 participants had an incident cardiovascular event. At baseline, cardiovascular risk factors, pre-existing cardiovascular disease and levels of NT-proBNP were evaluated.. Raised plasma NT-proBNP levels were associated with these classical cardiovascular risk factors: increased duration of diabetes, use of insulin, raised BMI, reduced HDL-cholesterol, reduced renal function and use of lipid-lowering and anti-hypertensive medication (all p < 0.05). In the prospective analysis, NT-proBNP was strongly associated with subsequent risk of all cardiovascular disease events (HR per one SD increase in NT-proBNP 1.39; 95% CI 1.10, 1.75), independent of cardiovascular risk factors traditionally used to predict vascular events. NT-proBNP was also independently associated with incident coronary artery disease events (1.48, 95% CI 1.10, 1.98). The addition of NT-proBNP to multivariate models improved the C-index by 0.019 for the 'hard' cardiac endpoint (fatal and non-fatal myocardial infarction).. In older people with type 2 diabetes, NT-proBNP is associated with the development of coronary and cerebrovascular events, independent of a wide range of other vascular and metabolic risk factors, and may prove a useful addition to current vascular risk scores in diabetes populations.

Topics: Aged; Biomarkers; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Prospective Studies; Risk Assessment; Risk Factors

Circulating levels of N-terminal fragment of probrain natriuretic peptide (NT-proBNP) are established as a risk factor for cardiovascular disease and mortality in patients with diabetes, as well as in the general population. We sought to examine the possibility of NT-proBNP as a biomarker of microvascular complications in patients with type 2 diabetes.. In total, 277 outpatients with type 2 diabetes were consecutively enrolled as a hospital cohort. Two hundred and seventeen of these patients (132 males; mean age, 63.4 years) were designated as cases with any of the diabetic complications (retinopathy, neuropathy, nephropathy, ischemic heart disease, strokes, peripheral artery disease), and 60 (42 males; mean age, 54.1 years) were set as controls without clinical evidence of diabetic complications. Diabetic complications were evaluated by medical record and routine laboratory examinations. NT-proBNP was measured and investigated with regard to the associations with diabetic complications.. Mean NT-proBNP levels were significantly higher in patients with any of the diabetic complications (59 versus 33 pg/mL; P<0.0001). In logistic regression analysis, NT-proBNP levels >79 pg/mL, which was the highest tertile, were independently associated with a 5.04 fold increased risk of all complications (P<0.0051) compared to the lowest tertile (NT-proBNP levels <31 pg/mL). Odd ratios of cardiovascular disease and nephropathy, neuropathy, and retinopathy were 9.33, 6.23, 6.6 and 13.78 respectively, in patients with NT-proBNP values in the highest tertile (>79 pg/mL), independently of age, sex, duration of diabetes or other risk factors, such as body mass index or hemoglobin A1c. In addition, NT-proBNP levels were associated with surrogate markers of atherosclerosis, such as brachial-ankle pulse wave velocity (r=0.449, P<0.0001) and left ventricular hypertrophy (r=0.212, P<0.001).. In this hospital-based cohort of type 2 diabetes, the NT-proBNP levels were associated with systemic atherosclerosis and comorbid diabetic microvascular as well as macrovascular complications. It is useful to stratify high-risk diabetic patients by measuring NT-proBNP and to start comprehensive care for preventing the progression of diabetic complications. It is necessary to elucidate the underlying mechanism for the progression of diabetic complications represented by an elevation of NT-proBNP and to demonstrate the ability of NT-proBNP as a predictive global biomarker for diabetic complications in Japanese type 2 diabetic patients.

Topics: Aged; Asian People; Atherosclerosis; Biomarkers; Case-Control Studies; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Disease Progression; Female; Humans; Japan; Logistic Models; Male; Microcirculation; Middle Aged; Natriuretic Peptide, Brain; Odds Ratio; Peptide Fragments; Predictive Value of Tests; Prognosis; Risk Factors; Up-Regulation

Asymptomatic systolic dysfunction of the left ventricle (LV) refers to patients without current clinical symptoms of heart failure.. 1. Analysis of echocardiographic parameters in patients with stable angina pectoris without symptoms of heart failure and their changes in two years time 2. Determine the importance of NT-proBNP for early detection of asymptomatic heart dysfunction in patients with stable angina pectoris and its influence on the prognosis in two years 3. Analysis of the relationship between the degree of the left ventricular diastolic dysfunction and co-morbidities and selected echocardiographic parameters 4. Significance of prognostic selected echocardiographic parameters (E/ Vp, E/E', Ar) in patients with stable angina pectoris without any symptoms of heart failure.. The study included 57 patients with stable ischemic heart disease, no history of myocardial infarction: including 35 men (61.4%) aged 35-56 years (mean 51.08 +/- 4.01 years) hospitalized in the Department of Coronary Artery Disease, Institute of Cardiology, Jagiellonian University in Krakow. Analysis after two years involved 56 patients (1 patient died after a year of observation).. Patients were evaluated 2x: before and after 2 years (assessment of clinical status: physical examination, the severity of angina and physical examination, atherosclerotic risk factors, ECG, lipid profile, plasma NT-proBNP). Patients were divided into three groups: Group A, patients with LV normal function (32 patients), Group B - with impaired diastolic function (22), Group C - with impaired systolic and diastolic function (EF < or = 50%, as measured by Simpson; 3 patients).. Subgroups of respondents ABC did not differ significantly with respect to age, sex and risk fac- tors of atherosclerosis. There was a significant correlation between the type of LV dysfunction and indicators of elevated end diastolic pressure in LV: E/Vp (p = 0.0002), E/E' (p = 0.0006), Ar (p = 0.034) and the propagation velocity Vp (0 = 0.001). There was a significant correlation between systolic and diastolic heart dysfunction and the levels of NT-proBNP (p = 0.018). After 2 years, patients with deterioration of heart function in group A noticed a significant correlation between occurrence of diastolic dysfunction and presence of diabetes mellitus type II (p = 0.01). Conclusions: 1. Elevated levels of NT-proBNP indicates the impairment of systolic andlor diastolic asymptomatic patients. NT-proBNP is therefore important for early detection of asymptomatic cardiac dysfunction in patients with stable angina pectoris. 2. In patients with stable angina pectoris without symptoms of heart failure: the value of E/Vp > or = 1.5 and E/E '> or = 8 can be the marker of more advanced coronary atherosclerosis, manifested by three-vessel disease or stenosis of the left main coronary artery.

Topics: Adult; Angina Pectoris; Biomarkers; Diabetes Mellitus, Type 2; Echocardiography; Electrocardiography; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Ventricular Dysfunction, Left

Hypertension stimulates the sympathetic nervous system and this phenomenon is exacerbated by diabetes mellitus. We investigated the effects of cilnidipine, an N/L-type calcium channel blocker, on aspects of this system in patients with type 2 diabetes mellitus.. In 33 hypertensive patients with type 2 diabetes mellitus treated with a calcium channel blocker other than cilnidipine, we evaluated the influence of switching to cilnidipine on blood pressure, heart rate, catecholamine, plasma renin and aldosterone concentration, brain natriuretic peptide, urine liver-type fatty acid binding protein, and urinary albumin excretion ratio in the same patients by a cross-over design. Other biochemical parameters were also evaluated.. Switching to cilnidipine did not change blood pressure but caused reduction in catecholamine concentrations in blood and urine and plasma aldosterone concentration, accompanied by significant reduction in brain natriuretic peptide, urine liver-type fatty acid binding protein, and albumin excretion ratio. These parameters other than brain natriuretic peptide were significantly increased after cilnidipine was changed to the original calcium channel blocker.. In 33 hypertensive patients with type 2 diabetes mellitus, compared to other calcium channel blockers, cilnidipine suppressed sympathetic nerve activity and aldosterone, and significantly improved markers of cardiorenal disorders. Therefore, cilnidipine may be an important calcium channel blocker for use in combination with renin-angiotensin-aldosterone system inhibitors when dealing with hypertension complicated with diabetes mellitus.

Topics: Aged; Aged, 80 and over; Aldosterone; Blood Pressure; Calcium Channel Blockers; Diabetes Mellitus, Type 2; Dihydropyridines; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Heart Rate; Humans; Hypertension; Kidney; Male; Middle Aged; Natriuretic Peptide, Brain; Prognosis; Renin-Angiotensin System; Sympathetic Nervous System

Few data are available to assess whether a low-moderate reduction in estimated glomerular filtration rates (eGFR) has a role per se on cardiovascular (CV) mortality or other biomarkers such as NT-proBNP allow to explain such association.. In a prospective study including 1,645 type 2 diabetic subjects of the population-based Casale Monferrato Study, who had no clinical evidence of heart failure and eGFR >45 ml/min/1.73 m2, we examined 6 years CV mortality. Multivariate Cox proportional hazards modeling were used to estimate the effect of NT-proBNP on the association between eGFR and mortality, independently of baseline CV risk factors, albumin excretion rate (AER) and C-reactive protein (CRP). During follow-up, 327 people died (149 of CV diseases) out of 8334.5 person-years. Compared to eGFR≥90 ml/min/1.73 m2, values of 60-89 and 45-59 ml/min/1.73 m2 conferred a fully adjusted hazard ratios (HRs) of CV mortality of 1.74 (1.08-2.82) and 1.95 (1.03-3.68), respectively. After further adjustment for NT-proBNP, however, HRs were no longer significant (HRs 1.42, 0.83-2.42 and 1.22, 0.59-2.51). In this model, HR for logNT-proBNP was 1.84 (1.52-2.22). Adding NT-proBNP to the model improved the C-statistic of CV mortality from 0.79 (0.76-0.83) to 0.84 (0.81-0.87), yielded an IDI of 0.03 (p = 0.02), and a NRI of 0.44 (p = 0.016).. In diabetic people a modest reduction in renal function increased 6-year CV mortality independently of albuminuria. This association, however, was mainly explained by the effect of NT-proBNP, that remained the strongest prognostic marker for a worse CV outcome, even after adjustment for other CV risk factors and pre-existing CVD.

Topics: Aged; Diabetes Mellitus, Type 2; Female; Glomerular Filtration Rate; Heart Failure; Humans; Male; Middle Aged; Mortality; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Proportional Hazards Models; Renal Insufficiency

Topics: Acute Disease; Atrial Fibrillation; Cardiomegaly; Diabetes Mellitus, Type 2; Diuretics; Heart Failure; Hemorrhage; Humans; Hydrostatic Pressure; Hypertension; Leukocytosis; Lung Diseases; Lung Diseases, Interstitial; Male; Middle Aged; Natriuretic Peptide, Brain; Pulmonary Edema; Sleep Apnea Syndromes; Smoking; Tomography, X-Ray Computed; Ultrasonography

To study whether N-terminal probrain natriuretic peptide (NT-proBNP) is a short-term independent predictor of both all-cause and cardiovascular (CV) mortality in type 2 diabetic patients and to establish whether albuminuria and C-reactive protein (CRP) affect this relationship.. The prospective study included 1,825 type 2 diabetic patients from the population-based cohort of the Casale Monferrato study. CV risk factors, preexisting CVD, and NT-proBNP levels were evaluated at baseline. All-cause and CV mortality were assessed 5.5 years after baseline examination. Multivariate Cox proportional hazards modeling was used to estimate mortality hazard ratios (HRs).. During the follow-up period, 390 people died (175 for CVD) out of 9,101 person-years of observations. A significantly increased mortality risk by quartiles of NT-proBNP was observed (test for trend, P < 0.001). NT-proBN P values >91 pg/mL conferred HRs of 2.05 (95% CI 1.47-2.86) for all-cause and 4.47 (2.38-8.39) for CV mortality, independently of CV risk factors, including CRP and albumin excretion rate (AER). The association was also significant for modest rises in NT-proBNP levels and in patients without microalbuminuria and CVD at baseline (upper quartiles HRs 3.82 [95% CI 1.24-13.75]) and 3.14 [1.00-9.94]). Albuminuria and NT-proBNP had an additive effect on mortality, though the association was stronger for NT-proBNP.. NT-proBNP is a strong independent predictor of short-term CV mortality risk in elderly people with type 2 diabetes, including those without preexisting CVD. This association is evident even in people with slightly increased values, is not modified by CRP, and is additive to that provided by AER.

Topics: Aged; Aged, 80 and over; C-Reactive Protein; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies

Dipeptidyl peptidase IV (DPP IV) is a key enzyme in B-type natriuretic peptide processing. DPP IV was never studied in human heart failure (HF). We aimed to measure DPP IV concentration in acute HF and determine its association with mortality.. Patients hospitalized with acute HF were eligible. We excluded patients with acute coronary syndromes. A discharge blood sample was collected from all patients and they were followed for a 6-month period. Outcome was HF death. Patients were compared across DPP IV quartiles. A Cox regression analysis was used to assess the prognostic power of DPP IV. We studied 164 patients. Median age was 78 years, 48.8% were men, and 63 had type 2 diabetes and 59.1% had left ventricular systolic dysfunction. Quartiles of DPP IV were <215.2; ≥ 215.2 and <269.3; ≥ 269.3 and <348.6; and ≥ 348.6 ng/mL; groups were homogenous between them. Seventeen patients died. Patients with DPP IV in the last quartile had a hazard ratio of HF death up to 6 months of 2.89, 95% confidence interval, 1.11-7.46. Association was B-type natriuretic peptide independent.. Discharge DPP IV ≥ 348.6 ng/mL conferred an approximately 3-fold higher risk of 6-month HF death. Further studies would be important to understand the role of DPP IV in HF.

Topics: Acute Disease; Aged; Aged, 80 and over; Comorbidity; Diabetes Mellitus, Type 2; Dipeptidyl Peptidase 4; Female; Follow-Up Studies; Heart Failure; Hospitals, Urban; Humans; Male; Natriuretic Peptide, Brain; Patient Discharge; Pilot Projects; Portugal; Risk Factors; Survival Analysis; Up-Regulation; Ventricular Dysfunction, Left

Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Diabetes Mellitus, Type 2; Female; Heart Diseases; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments

In patients with heart failure plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) levels are correlated to urine neutrophil gelatinase-associated lipocalin (NGAL) levels. We prospectively evaluated the relationship among glomerular filtration rate (eGFR), urine albumin-to-creatinine ratio (ACR), urine and serum NGAL and NT-proBNP levels in 20 type II diabetic patients with macroalbuminuria at 4-month intervals.. Compared with 20 age, gender-matched healthy controls, diabetic patients had higher urine and serum NGAL, serum NT-proBNP and lower eGFR. The eGFR of the patients at the baseline, the 4th and the 8th month were 29.6 ± 12.0, 27.8 ± 13.7 and 22.9 ± 10.4 mL/min/1.73 m(2), respectively. No significant change in urine NGAL levels was detected (p > 0.05), whereas there were significant increases in NT-proBNP, serum NGAL and urine ACR and significant decrease in eGFR as the study progressed (p < 0.05). Both the baseline and the 4th month urine ACR were positively correlated to NT-proBNP levels measured at the same periods (r: 0.451; p: 0.046; r: 0.489; p: 0.029 respectively). In all measurements, urine ACR was negatively correlated to serum albumin levels measured at the same periods (r: -0.792; p: 0.000; r: -0.716; p: 0.000; r: -0.531; p: 0.016 respectively). None of eGFR measurements was correlated with NT-proBNP (p > 0.05). Neither serum NGAL nor urinary NGAL levels are associated with NT-proBNP (p > 0.05).. Our findings show an association between NT-proBNP and proteinuria in type II diabetic patients with macroalbuminuria but not with serum and urine NGAL.

Topics: Acute-Phase Proteins; Adult; Aged; Case-Control Studies; Creatinine; Diabetes Complications; Diabetes Mellitus, Type 2; Female; Glomerular Filtration Rate; Humans; Lipocalin-2; Lipocalins; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Pilot Projects; Proteinuria; Proto-Oncogene Proteins

Individuals with type 2 diabetes (T2DM) are at increased risk of cardiovascular disease, including heart failure (HF). In patients with T2DM elevated serum concentrations of the N-terminal fragment of pro-B-type natriuretic peptide (NT-proBNP) correlate with cardiovascular morbidity and mortality. We aimed to identify predictors of increased serum NT-proBNP levels in patients with T2DM.. The study included 185 patients with T2DM treated with either oral antidiabetic agents (49.7%) or insulin (17.8%), or both (32.5%). We divided the patients into two groups: with high (>200 pg/mL) and low (≤200 pg/mL) NT-proBNP concentrations.. We found differences between the patients with high and low NT-proBNP levels including age, prevalence of dyslipidemia and HF, history of previous myocardial infarction (MI), heart rate, hemoglobin level, platelet count, creatinine, urea and uric acid concentrations, use of beta-blockers, loop diuretics, metformin and insulin. In a multivariate analysis metformin was a negative predictor of increased NT-proBNP concentration. Age, history of HF and decreased estimated glomerular filtration rate (eGFR) were positive predictors. We found no correlation between NT-proBNP serum concentration and insulin treatment or history of coronary artery disease or MI.. Metformin correlates with lower concentrations of NT-proBNP in patients with T2DM.

Topics: Adrenergic beta-Antagonists; Aged; Atherosclerosis; Biguanides; Cardiovascular Diseases; Coronary Artery Disease; Diabetes Mellitus, Type 2; Diuretics; Female; Heart Failure; Humans; Hypoglycemic Agents; Insulin; Male; Metformin; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prevalence; Risk Factors

N-terminal pro-brain natriuretic peptide (NT-proBNP), which is a useful biomarker of chronic heart failure, has been shown to be a strong predictor of cardiovascular mortality. The aim of this study was to evaluate the relationships between NT-proBNP and markers of subclinical atherosclerosis in patients with type 2 diabetes. Relationships of NT-proBNP to pulse wave velocity (PWV) or ankle-brachial index (ABI) as well as to various parameters, including body mass index, blood pressure, serum lipid concentration, serum uric acid concentration, and glycemic control (hemoglobin A1c), age, hemoglobin, serum creatinine concentration, severity of diabetic nephropathy or retinopathy, current treatment of diabetes, cardiothoracic ratio on chest radiograph, presence of left ventricular hypertrophy and/or ST-T changes evaluated by electrocardiograph, smoking status and presence of cardiovascular disease were investigated in 323 consecutive patients with type 2 diabetes. Log (NT-proBNP) correlated positively with PWV (r = 0.283, p < 0.0001) and correlated negatively with ABI (r = -0.144, p = 0.0094). Multiple regression analysis demonstrated that age (β = 0.200, p = 0.0033), systolic blood pressure (β = 0.246, p < 0.0001), total cholesterol (β = -0.135, p = 0.0326), uric acid (β = 0.133, p = 0.0462), creatinine (β = -0.184, p = 0.0122), smoking status (β = -0.129, p = 0.0499) and log (NT-proBNP) (β = 0.177, p = 0.0149) were independently correlated with PWV and that systolic blood pressure (β = -0.145, p = 0.0310), log triglyceride (β = -0.151, p = 0.0397) and log (NT-proBNP) (β = -0.207, p = 0.0094) were independently correlated with ABI. In conclusion, NT-proBNP could be a marker of subclinical atherosclerosis in patients with type 2 diabetes.

Topics: Aged; Ankle Brachial Index; Asymptomatic Diseases; Atherosclerosis; Biomarkers; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Hemodynamics; Humans; Linear Models; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Pulse Wave Analysis

Ginseng (Araliaceae) has multiple pharmacological actions because of its diverse phytochemical constituents. The aims of the present study are to evaluate the preventive effects of North American ginseng on diabetic retinopathy and cardiomyopathy and to delineate the underlying mechanisms of such effects. Models of both type 1 (C57BL/6 mice with streptozotocin-induced diabetes) and type 2 diabetes (db/db mice) and age-matched and sex-matched controls were examined. Alcoholic ginseng root (200 mg/kg body weight, daily oral gavage) extract was administered to groups of both type 1 and type 2 diabetic mice for 2 or 4 months. Dysmetabolic state in the diabetic mice was significantly improved by ginseng treatment. In both the heart and retina of diabetic animals, ginseng treatment significantly prevented oxidative stress and diabetes-induced upregulations of extracellular matrix proteins and vasoactive factors. Ginseng treatment in the diabetic animals resulted in enhancement of stroke volume, ejection fraction, cardiac output, and left ventricle pressure during systole and diastole and diminution of stroke work. In addition, mRNA expressions of atrial natriuretic factor and brain natriuretic factor (molecular markers for cardiac hypertrophy) were significantly diminished in ginseng-treated diabetic mice. These data indicate that North American ginseng prevents the diabetes-induced retinal and cardiac biochemical and functional changes probably through inhibition of oxidative stress.

Topics: Animals; Atrial Natriuretic Factor; Blood Glucose; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Diabetic Cardiomyopathies; Diabetic Retinopathy; Extracellular Matrix Proteins; Heart; Male; Mice; Mice, Inbred C57BL; Natriuretic Peptide, Brain; Oxidative Stress; Panax; Phytotherapy; Plant Extracts; Plant Roots; Retina

Animal data suggest that natriuretic peptides play an important role in energy metabolism, but prospective studies evaluating a relationship between these peptides and type 2 diabetes mellitus (T2DM) in humans are few and results are conflicting.. We used a prospective case-cohort approach (n = 491 T2DM cases, n = 561 reference subcohort) within the Women's Health Study to evaluate baseline N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations and the risk of incident T2DM. We also tested for associations between 4 common variants in the natriuretic peptide A and B genes (NPPA and NPPB) and NT-proBNP concentrations (n = 458) and incident T2DM (n = 1372 cases among 22 607 women).. Case subjects had higher median baseline body mass index (29.4 vs 25.0 kg/m(2), P < 0.001) and lower baseline median (interquartile range) NT-proBNP concentrations [46.8 ng/L (26.1-83.2) vs 66.7 ng/L (39.3-124.7), P < 0.001]. In proportional hazards models adjusting for established diabetes risk factors, women in the highest quartile of baseline NT-proBNP concentration (≥ 117.4 ng/L) had a 49% reduction in risk of T2DM [hazard ratio (HR) 0.51, 0.30-0.86, P = 0.01] relative to those in the lowest quartile. Two of the 4 tested variants in NPPA and NPPB (rs632793, rs198389) were associated with increased NT-proBNP concentrations and reduced risk of T2DM. For example, each copy of the minor allele of rs632793 was associated with increased NT-proBNP [β (SE) = 0.201 (0.063), P < 0.01] and decreased T2DM risk (HR 0.91, 0.84-0.989, P = 0.026).. NT-proBNP concentrations that are high, but still within the reference interval, associate with reduced risk of incident diabetes in women and support a favorable role for natriuretic peptides in the prevention of T2DM.

Topics: Atrial Natriuretic Factor; Body Mass Index; Diabetes Mellitus, Type 2; Female; Humans; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Polymorphism, Single Nucleotide; Prospective Studies; Risk

The serum N-terminal fragment of pro brain natriuretic peptide (NT-proBNP) level in type 2 diabetic subjects with or without diabetic nephropathy (DN) is still unclear. We aimed to evaluate the relationship between serum NT-proBNP levels and different stages of diabetic nephropathy, and identify probable factors predicting serum NT-proBNP level.. This cross-sectional study included 20 normoalbuminuric (Group-I), 28 microalbuminuric (Group-II), 20 macroalbuminuric type 2 diabetic patients (Group-III), and 20 healthy volunteers (Group-IV). Serum NT-proBNP levels were measured with highly sensitive and specific immunoassay.. Mean NT-proBNP levels were 32 ± 55, 91 ± 95, 331 ± 297, 42 ± 34 pg/ml for Groups I-IV, respectively. When patients with LVH were excluded, mean logNT-proBNP was still significantly higher in Group-III than all other groups. The three diabetic groups were similar in age, BMI, HbA1c, fasting serum glucose, and GFR. In a multivariate linear regression model, adjusting for factors significantly correlated with NT-proBNP levels, the patient group, presence of LVH, and hemoglobin remained as an independent predictor of serum NT-proBNP. These variables explained 68% of the variability of NT-proBNP (adjusted R(2)=0.683).. Mean serum NT-proBNP level of macroalbuminuric diabetic patients was higher than normoalbuminuric and microalbuminuric diabetic patients, and healthy control subjects even after exclusion of LVH. NT-proBNP may be a useful and predictive marker of diabetic nephropathy.

Topics: Adult; Biomarkers; Case-Control Studies; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Female; Humans; Immunoassay; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Serum Albumin

Coronary artery disease (CAD) is the major cause of morbidity and mortality in type 2 diabetic patients. Severe vitamin D deficiency has been shown to predict cardiovascular mortality in type 2 diabetic patients.. We investigated the association among severe vitamin D deficiency, coronary calcium score (CCS), and asymptomatic CAD in type 2 diabetic patients with elevated urinary albumin excretion rate (UAER) >30 mg/24 h. This was a cross-sectional study including 200 type 2 diabetic patients without a history of CAD. Severe vitamin D deficiency was defined as plasma 25-hydroxyvitamin D (p-25[OH]D3) <12.5 nmol/L. Patients with plasma N-terminal pro-brain natriuretic peptide >45.2 ng/L or CCS ≥400 were stratified as being high risk for CAD (n= 133). High-risk patients were examined by myocardial perfusion imaging (MPI; n = 109), computed tomography angiography (n = 20), or coronary angiography (CAG; n = 86). Patients' p-25(OH)D3 levels were determined by high-performance liquid chromatography/tandem mass spectrometry.. The median (range) vitamin D level was 36.9 (3.8-118.6) nmol/L. The prevalence of severe vitamin D deficiency was 9.5% (19/200). MPI or CAG demonstrated significant CAD in 70 patients (35%). The prevalence of CCS ≥400 was 34% (68/200). Severe vitamin D deficiency was associated with CCS ≥400 (odds ratio [OR] 4.3, 95% CI [1.5-12.1], P = 0.005). This association persisted after adjusting for risk factors (4.6, 1.5-13.9, P = 0.007). Furthermore, severe vitamin D deficiency was associated with asymptomatic CAD (adjusted OR 2.9, 1.02-7.66, P = 0.047).. In high-risk type 2 diabetic patients with elevated UAER, low levels of vitamin D are associated with asymptomatic CAD.

Topics: Adult; Aged; Albuminuria; Calcifediol; Calcinosis; Coronary Artery Disease; Cross-Sectional Studies; Denmark; Diabetes Mellitus, Type 2; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Risk Factors; Vitamin D Deficiency

Hyperuricemia is a risk factor for cardiovascular events and renal insufficiency. It correlates to intima-media thickness and microalbuminuria. In this study we evaluated uric acid as an independent marker for cardiac events in patients with diabetes.. In a prospective observational study we recruited 494 patients with diabetes. Patients were then followed for 12.8 months (mean follow-up) and hospitalizations as a result of cardiac events (ischaemic heart disease, arrhythmias, heart failure) were recorded.. The median duration of diabetes was 11 ± 10.35 years. Patients were in the mean 60 ± 13 years old and mean HbA(1c) was 62 ± 13 mmol/mol (7.8 ± 3.3%). At baseline, mean uric acid was 321.2 ± 101.1 μmol/l (range 101.1-743.5 μmol/l), median N-terminal pro-B-type natriuretic peptide was 92 ± 412 pg/ml and median urinary albumin to creatinine ratio was 8 ± 361 mg/g; Uric acid significantly correlated to N-terminal pro-B-type natriuretic peptide (r = 0.237, P < 0.001) and urinary albumin:creatinine ratio (r = 0.198, P < 0.001). In a Cox regression model, including age, estimated glomerular filtration rate, gender, systolic blood pressure, smoking and alcohol consumption, uric acid was the best predictor of cardiac events (hazard ratio 1.331, confidence interval 1.095-1.616, P = 0.04). However, uric acid lost its prognostic value when the natural logarithm of N-terminal pro-B-type natriuretic peptide was added to the model.. Serum uric acid is a predictor of cardiac events and correlates to N-terminal pro-B-type natriuretic peptide and albuminuria, underscoring the importance of uric acid as a cardiovascular risk marker in patients with diabetes.

Topics: Albuminuria; Atherosclerosis; Biomarkers; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Nephropathies; Female; Glycated Hemoglobin; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Prospective Studies; Renal Insufficiency; Risk Factors; Uric Acid

Early diagnosis of cardiovascular disease in diabetic patients may be important to introduce treatment early. Echocardiography is a method used to show the ventricular functions. A ventricular hormone, BNP is used to identify the changes in the ventricular function in early period. NT-proBNP which is a more stable compound with a longer half-life is used in measurement of BNP.. Left ventricular diastolic dysfunction (LVDD) was detected and NT-proBNP levels were measured in forty-four asymptomatic patients with ages of 30-70 and type 2 DM and control group consisted of 40 healthy individuals from the same age group.. NT-proBNP levels were found as 566.7 ± 738.5 pg/ml in the diabetics with LVDD detected, 166.3 ± 137.1 pg/ml in the diabetics without LVDD and 134.5 ± 77.2 pg/ml in the control group. Levels of NT-proBNP were significantly higher in the group with left ventricular diastolic dysfunction (p<0.05). However, when the levels of NT-proBNP in the diabetic patients without LVDD were compared with the controls, the difference was not significant (p>0.05). NT-proBNP levels were found significantly higher in LVDD group compared to the controls without a difference between the ejection fractions (p<0.05).. High levels of NT-proBNP was correlated tissue Doppler echocardiography findings in type 2 DM patients with preserved ejection fraction.

Topics: Adult; Aged; Diabetes Mellitus, Type 2; Echocardiography, Doppler; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Ventricular Dysfunction, Left

(-)-Epicatechin (Epi), a flavanol in cacao stimulates mitochondrial volume and cristae density and protein markers of skeletal muscle (SkM) mitochondrial biogenesis in mice. Type 2 diabetes mellitus (DM2) and heart failure (HF) are diseases associated with defects in SkM mitochondrial structure/function. A study was implemented to assess perturbations and to determine the effects of Epi-rich cocoa in SkM mitochondrial structure and mediators of biogenesis. Five patients with DM2 and stage II/III HF consumed dark chocolate and a beverage containing approximately 100 mg of Epi per day for 3 months. We assessed changes in protein and/or activity levels of oxidative phosphorylation proteins, porin, mitofilin, nNOS, nitric oxide, cGMP, SIRT1, PGC1α, Tfam, and mitochondria volume and cristae abundance by electron microscopy from SkM. Apparent major losses in normal mitochondria structure were observed before treatment. Epi-rich cocoa increased protein and/or activity of mediators of biogenesis and cristae abundance while not changing mitochondrial volume density. Epi-rich cocoa treatment improves SkM mitochondrial structure and in an orchestrated manner, increases molecular markers of mitochondrial biogenesis resulting in enhanced cristae density. Future controlled studies are warranted using Epi-rich cocoa (or pure Epi) to translate improved mitochondrial structure into enhanced cardiac and/or SkM muscle function.

Topics: Aged; Beverages; Biomarkers; Biopsy; Cacao; California; Candy; Catechin; Diabetes Mellitus, Type 2; Functional Food; Glycated Hemoglobin; Heart Failure; Humans; Lipids; Middle Aged; Mitochondria, Muscle; Mitochondrial Proteins; Natriuretic Peptide, Brain; Quadriceps Muscle; Time Factors; Treatment Outcome

Intensive multifactorial treatment aimed at prevention of cardiovascular (CV) disease may reduce left ventricular (LV) echocardiographic abnormalities in diabetic subjects. Plasma N-terminal (NT)-proBNP predicts CV mortality in diabetic patients but the association between P-NT-proBNP and the putative residual abnormalities in such patients are not well described. This study examined echocardiographic measurements of LV hypertrophy, atrial dilatation and LV dysfunction and their relation to P-NT-proBNP levels or subclinical coronary artery disease (CAD) in type 2 diabetic patients with microalbuminuria receiving intensive multifactorial treatment.. Echocardiography including tissue Doppler imaging and P-NT-proBNP measurements were performed in 200 patients without prior CAD. Patients with P-NT-proBNP > 45.2 ng/L and/or coronary calcium score ≥ 400 were stratified as high risk patients for CAD(n = 133) and examined for significant CAD by myocardial perfusion imaging and/or CT-angiography and/or coronary angiography.. LV mass index was 41.2 ± 10.9 g/m2.7 and 48 (24%) patients had LV hypertrophy. LA and RA dilatation were found in 54(27%) and 45(23%) patients, respectively, and LV diastolic dysfunction was found in 109(55%) patients. Patients with increased P-NT-proBNP levels did not have more major echocardiographic abnormalities. In 70(53%) of 133 high risk patients significant CAD was demonstrated and patients with LV hypertrophy had increased risk of significant CAD(adjusted odd ratio[CI] was 4.53[1.14-18.06]).. Among asymptomatic type 2 diabetic patients with microalbuminuria that received intensive multifactorial treatment, P-NT-proBNP levels is not associated with echocardiographic abnormalities. LV diastolic dysfunction was frequently observed, whereas LV hypertrophy was less frequent but associated with significant CAD.

Topics: Aged; Albuminuria; Asymptomatic Diseases; Biomarkers; Coronary Angiography; Coronary Artery Disease; Cross-Sectional Studies; Denmark; Diabetes Complications; Diabetes Mellitus, Type 2; Echocardiography, Doppler; Female; Heart Atria; Humans; Hypertrophy, Left Ventricular; Linear Models; Logistic Models; Male; Middle Aged; Multivariate Analysis; Myocardial Perfusion Imaging; Natriuretic Peptide, Brain; Odds Ratio; Peptide Fragments; Predictive Value of Tests; Risk Assessment; Risk Factors; Tomography, X-Ray Computed; Ventricular Dysfunction, Left

Atrial fibrillation (AF) is a highly prevalent cardiac arrhythmia in clinical practice, affecting approximately 2.3 million residents of the United States and 4.5 million residents of the European Union. It is unclear whether plasma free fatty acids (FFAs) influence the risk of AF in older adults. The aim of this study was to prospectively examine the association between plasma FFAs and incident AF in a prospective cohort of 4,175 men and women ≥65 years old from the Cardiovascular Health Study. Plasma concentrations of FFAs were measured 2 times during the 1992 to 1993 examination. Incident AF was ascertained based on study electrocardiographic and hospitalization records during follow-up. We used Cox regression to estimate relative risks of AF. Average age at baseline was 74.6 ± 5.1 years. During a mean follow-up of 10.0 years, 1,041 new cases of AF occurred. Crude incidence rates of AF were 23.7, 23.3, 23.9, and 29.7 cases/1,000 person-years across consecutive quartiles of plasma FFAs. There was a positive association between plasma FFAs and risk of AF. Multivariable adjusted hazard ratios (95% confidence intervals) for incident AF were 1.00 (referent), 1.02 (0.85 to 1.21), 1.05 (0.88 to 1.26), and 1.29 (1.08 to 1.55) from the lowest to highest quartiles of FFAs, respectively. In a secondary analysis restricted to the first 5 years of follow-up, this association persisted. In conclusion, our data show an increased risk of AF with higher plasma FFAs in community-dwelling older adults.

Topics: Aged; Atrial Fibrillation; C-Reactive Protein; Diabetes Mellitus, Type 2; Fatty Acids, Nonesterified; Female; Follow-Up Studies; Humans; Hypertension; Incidence; Lipoproteins, HDL; Lipoproteins, LDL; Male; Natriuretic Peptide, Brain; Obesity; Peptide Fragments; Prospective Studies; Sex Factors; Triglycerides; United States

The aim of this study was to assess the prevalence of (unknown) heart failure and left ventricular dysfunction in older patients with type 2 diabetes.. In total, 605 patients aged 60 years or over with type 2 diabetes in the south west of the Netherlands participated in this cross-sectional study (response rate 48.7%), including 24 with a cardiologist-confirmed diagnosis of heart failure. Between February 2009 and March 2010, the patients without known heart failure underwent a standardised diagnostic work-up, including medical history, physical examination, ECG and echocardiography. An expert panel used the criteria of the European Society of Cardiology to diagnose heart failure.. Of the 581 patients studied, 161 (27.7%; 95% CI 24.1%, 31.4%) were found to have previously unknown heart failure: 28 (4.8%; 95% CI 3.1%, 6.6%) with reduced ejection fraction, and 133 (22.9%; 95% CI 19.5%, 26.3%) with preserved ejection fraction. The prevalence of heart failure increased steeply with age. Heart failure with preserved ejection fraction was more common in women. Left ventricular dysfunction was diagnosed in 150 patients (25.8%; 95% CI 22.3%, 29.4%); 146 (25.1%; 95% CI 21.6%, 28.7%) had diastolic dysfunction.. This is the first epidemiological study that provides exact prevalence estimates of (previously unknown) heart failure and left ventricular dysfunction in a representative sample of patients with type 2 diabetes. Previously unknown heart failure and left ventricular dysfunction are highly prevalent. Physicians should pay special attention to 'unmasking' these patients.

Topics: Aged; Aged, 80 and over; Blood Glucose; Creatinine; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Echocardiography; Female; Glycated Hemoglobin; Heart Failure; Humans; Male; Mass Screening; Middle Aged; Natriuretic Peptide, Brain; Netherlands; Peptide Fragments; Prevalence; Stroke Volume; Ventricular Dysfunction, Left

In this study, we aimed to evaluate myocardial functions in patients with diabetes mellitus (DM) and impaired glucose tolerance (IGT). We also aimed to investigate the relationship between B-type natriuretic peptide (BNP) levels and myocardial performance index (Tei index) in these patients.. A total of 38 patients with DM, 34 patients with IGT, and 40 healthy volunteers were recruited to the study. Basal clinical and laboratory findings were recorded. BNP levels of all individuals were measured. Both conventional transthoracic and tissue Doppler echocardiogaphy were performed to all study participants.. B-type natriuretic peptide levels of the diabetic group were greater than in patients with IGT and the control group. BNP levels of the IGT group were also higher than the control group. Myocardial performance index values, measured by both the conventional method and tissue Doppler echocardiography, were significantly higher in the diabetic group than in the control group. There was a significant relationship between myocardial performance index and BNP levels.. Myocardial functions are disturbed in patients with DM and also in patients with IGT. BNP and myocardial performance index can be used in diabetic patients and in patients with IGT to define myocardial dysfunction.

Topics: Age Factors; Blood Glucose; Diabetes Mellitus, Type 2; Echocardiography; Female; Glucose Intolerance; Glycated Hemoglobin; Humans; Male; Middle Aged; Myocardium; Natriuretic Peptide, Brain; ROC Curve; Ventricular Dysfunction, Left

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Female; Glucose Intolerance; Humans; Male; Myocardium; Natriuretic Peptide, Brain; Ventricular Dysfunction, Left

Type 2 diabetes mellitus is associated with risk of congestive heart failure (CHF), cognitive dysfunction and depression. CHF itself is linked both to poor cognition and depression. The ventricular N-terminal pro-brain natriuretic peptide (NT-proBNP) is a marker of CHF, suggesting potential as a marker for cognitive impairment and/or depression. This was tested in the Edinburgh Type 2 Diabetes Study (ET2DS).. Cross-sectional analysis of 1066 men and women aged 60-75 with type 2 diabetes. Results from seven neuropsychological tests were combined in a standardised general cognitive ability factor, 'g'. A vocabulary-based test estimated pre-morbid cognitive ability. The Hospital Anxiety and Depression Scale (HADS) assessed possible depression. After adjustment for age and sex, raised plasma NT-proBNP was weakly associated with lower 'g' and higher depression scores (ß -0.09, 95% CI -0.13 to -0.03, p = 0.004 and ß 0.08, 95% CI 0.04 to 0.12, p<0.001, respectively). Comparing extreme quintiles of NT-proBNP, subjects in the highest quintile were more likely to have reduced cognitive ability (within the lowest tertile of 'g') and 'possible' depression (HADS depression ≥8) (OR 1.80; 95% CI: 1.20, 2.70; p = 0.005 and OR 2.18; 95% CI: 1.28, 3.71; p = 0.004, respectively). Associations persisted when pre-morbid ability was adjusted for, but as expected were no longer statistically significant following the adjustment for diabetes-related and vascular co-variates (β -0.02, 95% CI -0.07 to 0.03, p>0.05 for 'g'; β 0.03, 95% CI -0.02 to 0.07, p>0.05 for depression scores).. Raised plasma NT-proBNP was weakly but statistically significantly associated with poorer cognitive function and depression. The prospective phases of the ET2DS will help determine whether or not NT-proBNP can be considered a risk marker for subsequent cognitive impairment and incident depression and whether it provides additional information over and above traditional risk factors for these conditions.

Topics: Aged; Blood Pressure; Body Mass Index; Cholesterol; Cognition; Cross-Sectional Studies; Depression; Diabetes Mellitus, Type 2; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Neuropsychological Tests; Peptide Fragments

Heart failure is common in individuals with type 2 diabetes, and early detection of individuals at risk may offer opportunities for prevention. We aimed to explore 1) prospective associations of B-type natriuretic peptide (BNP) levels in a non-heart failure range with changes in markers of left ventricular (LV) function and 2) possible effect modification by type 2 diabetes in a population-based cohort.. Echocardiographic measurements were performed at baseline (2000-2001) and follow-up (2007-2009), together with standardized physical examinations and BNP measurements on 300 individuals (mean age 66 years, 32% with type 2 diabetes) of the longitudinal Hoorn Study. Multivariate linear regression analyses were performed to investigate associations of baseline BNP (<100 pg/mL) in individuals without prevalent heart failure at baseline with changes in LV mass index, LV ejection fraction, left atrial volume index, and ratio of early diastolic LV inflow velocity (E) to early diastolic lengthening velocity (e') (E/e').. In all individuals, higher BNP was associated with 8-year increases in left atrial volume index. Higher BNP was also associated with increasing LV mass index and E/e'. These associations were significantly stronger in individuals with type 2 diabetes compared with the nonsignificant associations in individuals without type 2 diabetes.. This 8-year follow-up study shows that higher BNP levels in a non-heart failure range were associated with an increased LV mass and deteriorated LV diastolic function, particularly in individuals with type 2 diabetes. This implies that the presence or absence of type 2 diabetes should be taken into account if BNP levels are used to assess future heart failure risk.

Topics: Aged; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Prospective Studies; Ventricular Function, Left

Elevated plasma N-terminal (NT)-proBNP from the heart as well as white matter hyperintensities (WMH) in the brain predict cardiovascular (CV) mortality in the general population. The cause of poor prognosis associated with elevated P-NT-proBNP is not known but WMH precede strokes in high risk populations. We assessed the association between P-NT-proBNP and WMH or brain atrophy measured with magnetic resonance imaging (MRI) in type 2 diabetic patients, and age-matched controls.. We measured P-NT-proBNP(ng/l) in 20 diabetic patients without prior stroke but with(n=10) or without(n=10) asymptomatic coronary artery disease(CAD) in order to include patients with a wide-ranging CV risk profile. All patients and 26 controls had a 3D MRI and brain volumes(ml) with WMH and brain parenchymal fraction(BPF), an indicator of brain atrophy, were determined.P-NT-proBNP was associated with WMH in linear regression analysis adjusted for CV risk factors(r=0.94, p=0.001) and with BPF in univariate analysis(r=0.57, p=0.009). Patients divided into groups of increased P-NT-proBNP levels were paralleled with increased WMH volumes(geometric mean[SD];(2.86[5.11] ml and 0.76[2.49] ml compared to patients with low P-NT-proBNP 0.20[2.28] ml, p=0.003)) and also when adjusted for age, sex and presence of CAD(p=0.017). The association was strengthened by CV risk factors and we did not find a common heart or brain specific driver of both P-NT-proBNP and WMH. Patients and particular patients with CAD had higher WMH, however no longer after adjustment for age and sex.. P-NT-proBNP was associated with WMH in type 2 diabetic patients, suggesting a linkage between heart and brain disease.

Topics: Adult; Aged; Atrophy; Biomarkers; Brain; Case-Control Studies; Chi-Square Distribution; Coronary Artery Disease; Diabetes Mellitus, Type 2; Female; Humans; Leukoencephalopathies; Linear Models; Magnetic Resonance Imaging; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Organ Size; Peptide Fragments; Risk Assessment; Risk Factors; Up-Regulation

The incidence of heart failure in type 2 diabetes is high and it has poorer prognosis when compared with patients without diabetes. Access to echocardiography is limited and alternative methods to identify early heart failure such as the measurement of natriuretic peptides levels have been proposed. However, their wide biological variation could limit their clinical utility. Our aim was to determine if the intrinsic biological variation of one of these peptides, N-terminal proBNP, is as wide in type 2 diabetes as it is in health and to calculate the critical difference values that could be utilised in clinical practice to ensure changes observed between two samples are due to intervention rather than to its biological variability.. 12 postmenopausal women with diet controlled type 2 diabetes and without heart failure were compared with 11 control postmenopausal women without diabetes. N-terminal proBNP levels were measured on 10 occasions. The biological variation was calculated according to Fraser's methods. The mean NT-proBNP level was similar in both groups (mean ± standard deviation; type 2 diabetes, 10.7 pmol/L± 8.5 versus 8.49±6.0 pmol/L, p = 0.42). The biological variation was also similarly wide. The critical difference in patients with type 2 diabetes was between -70% and ±236%.. Type 2 diabetes does not appear to significantly influence the marked biological variation of N-terminal proBNP in postmenopausal women. The critical difference values reported in this study could be used to titrate therapy or monitor response to interventions although the change required in between samples is wide and this might limit its utility.

Topics: Aged; Case-Control Studies; Diabetes Mellitus, Type 2; Female; Heart Failure; Humans; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Postmenopause

Several peptides, named adipokines, are produced by the adipose tissue. Among those, adiponectin (AD) is the most abundant. AD promotes peripheral insulin sensitivity, inhibits liver gluconeogenesis and displays anti-atherogenic and anti-inflammatory properties. Lower levels of AD are related to a higher risk of myocardial infarction and a worse prognosis in patients with coronary artery disease. However, despite a favorable clinical profile, AD increases in relation to worsening heart failure (HF); in this context, higher adiponectinemia is reliably related to poor prognosis. There is still little knowledge about how certain metabolic conditions, such as diabetes mellitus, modulate the relationship between AD and HF.We evaluated the level of adiponectin in patients with ischemic HF, with and without type 2 diabetes, to elucidate whether the metabolic syndrome was able to influence the relationship between AD and HF.. We demonstrated that AD rises in patients with advanced HF, but to a lesser extent in diabetics than in non-diabetics. Diabetic patients with reduced systolic performance orchestrated a slower rise of AD which began only in face of overt HF. The different behavior of AD in the presence of diabetes was not entirely explained by differences in body mass index. In addition, NT-proBNP, the second strongest predictor of AD, did not differ significantly between diabetic and non-diabetic patients. These data indicate that some other mechanisms are involved in the regulation of AD in patients with type 2 diabetes and coronary artery disease.. AD rises across chronic heart failure stages but this phenomenon is less evident in type 2 diabetic patients. In the presence of diabetes, the progressive increase of AD in relation to the severity of LV dysfunction is hampered and becomes evident only in overt HF.

Topics: Adiponectin; Aged; Coronary Artery Disease; Diabetes Mellitus, Type 2; Female; Heart Failure; Humans; Linear Models; Male; Middle Aged; Models, Cardiovascular; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments

1. Metformin is one of the most commonly used drugs for the treatment of Type 2 diabetes. Accumulating evidence suggests that metformin also has cardioprotective effects. In the present study, we investigated the cardioprotective effects of metformin and the mechanisms involved. 2. A rat model of chronic heart failure was established by permanent left coronary artery occlusion. Heart failure rats were randomly divided into four groups: (i) a saline-treated group given 4 mL/kg day via intragastric gavage; (ii) a metformin-treated group, given 100 mg/kg metformin once daily via intragastric gavage; (iii) a group treated with 5 mg/kg 5'-aminoimidazole-4-carboxyamide-ribonucleoside (AICAR), an AMP-activated protein kinase (AMPK) agonist, every second day; and (iv) a group treated with 100 mg/kg per day metformin + 20 mg/kg, i.p., compound C (an AMPK antagonist). After 4 weeks treatment, echocardiography was used to assess left ventricular (LV) dimensions and function. Expression of AMPK, endothelial nitric oxide synthase (eNOS) and transforming growth factor (TGF)-β1 was determined by reverse transcription-polymerase chain reaction and western blot analysis. 3. Metformin administration significantly improved cardiac function and LV remodelling, as evidenced by increases in LV systolic pressure and LV ejection fraction and decreases in LV end-diastolic diameter and LV end-systolic diameter. These beneficial effects of metformin were associated with increased AMPK and eNOS phosphorylation, as well as reductions in insulin, TGF-β1, basic fibroblast growth factor and tumour necrosis factor-α levels in the circulation and/or myocardium. 4. The results indicate that chronic low-dose metformin confers significant cardioprotective effects against chronic heart failure by activating the AMPK-eNOS pathway.

Topics: Aminoimidazole Carboxamide; AMP-Activated Protein Kinases; Animals; Blood Glucose; Diabetes Mellitus, Type 2; Echocardiography; Heart Failure; Hypoglycemic Agents; Insulin; Male; Metformin; Myocardium; Natriuretic Peptide, Brain; Nitric Oxide Synthase Type III; Random Allocation; Rats; Rats, Wistar; Ribonucleotides; Ventricular Function, Left; Ventricular Remodeling

High-mobility group box-1 (HMGB1) is a ligand for the receptor for advanced glycation endproducts (RAGE). An HMGB1-RAGE interaction has been implicated in cardiac dysfunction. We assessed the association of HMGB1 and RAGE isoforms with heart failure (HF) in diabetic and non-diabetic patients.. We assayed serum levels of HMGB1, cleaved RAGE (cRAGE), endogenous secretory RAGE (esRAGE), high-sensitivity C-reactive protein (hsCRP), and N-terminal pro-brain natriuretic peptide (NT-proBNP) in parallel with assessment of left ventricular volumes and function in 125 diabetic and 222 non-diabetic Chinese patients with chronic HF. Of the total, 79 diabetic patients without HF and 220 normal subjects served as diabetic and normal controls, respectively. Serum HMGB1, cRAGE, hsCRP, and NT-proBNP levels were higher and, in contrast, esRAGE levels lower in HF patients than in subjects without HF (for all; P < 0.01), with higher levels of cRAGE and hsCRP in diabetic HF vs. non-diabetic HF patients (P < 0.01). For HF patients-with or without diabetes-HMGB1 levels correlated positively with left ventricular end-diastolic and end-systolic volumes (r = 0.267 and r = 0.321, respectively) and NT-proBNP values (r = 0.497), and were inversely related to ejection fraction (r = -0.461; all P < 0.001). Serum cRAGE levels correlated with NT-proBNP values (r = 0.451) and New York Heart Association functional class (r = 0.402; both P < 0.001). Multivariable regression analysis revealed that HMGB1, cRAGE, and esRAGE were consistently associated with HF in diabetic and non-diabetic patients.. Heart failure patients have increased serum HMGB1 and cRAGE and decreased esRAGE levels, and these are related to the severity of HF in both diabetic and non-diabetic patients. Such associations are worth further investigation.

Topics: Adult; Aged; C-Reactive Protein; Case-Control Studies; China; Diabetes Mellitus, Type 2; Female; Glycation End Products, Advanced; Heart Failure; HMGB1 Protein; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Population Groups

Elevated plasma N-terminal (NT)-proBNP levels and coronary calcium score (CCS) not only predicts myocardial ischaemia and coronary artery stenosis but also adverse cardiovascular events and mortality in type 2 diabetic patients with an increased urinary albumin excretion rate (UAER), whereas low levels are associated with low frequency of coronary artery disease (CAD) and good prognosis. The underlying causes of poor prognosis in patients with elevated NT-proBNP are not known; thus, we investigated the role of putative asymptomatic CAD in type 2 diabetic patients with UAER >30 mg/24 h and elevated P-NT-proBNP and/or CCS.. We identified 200 type 2 diabetic patients without known CAD and with normal creatinine levels. Patients with P-NT-proBNP >45.2 ng/L (the median P-NT-proBNP value in this cohort and in accordance with our previous findings) and/or CCS ≥ 400 were stratified as high-risk patients for CAD (n = 133) and all other patients as low-risk patients (n = 67). High-risk patients were examined by myocardial perfusion imaging (MPI; n = 109) and/or computer tomography angiography (n = 20) and/or coronary angiography (CAG; n = 86).. All patients received intensive mulitifactorial intervention. In 70 of 133 (53%) high-risk patients, significant CAD was demonstrated by MPI and/or CAG, corresponding to 35% (70/200) of the total cohort. Among high-risk patients, CCS but not P-NT-proBNP was paralleled by increased prevalence of significant CAD and in the 86 patients where CAG was performed, a CCS <100 had a negative predictive value for coronary artery stenosis of 94% (P = 0.04).. Our study revealed that >50% of asymptomatic type 2 diabetic patients with UAER >30 mg/24 h had significant CAD based on risk stratification with P-NT-proBNP and CCS. This provides some explanation to the previously reported poor prognosis in these asymptomatic patients. Optimized cardio protective treatment in these patients is warranted.

Topics: Adult; Aged; Albuminuria; Algorithms; Biomarkers; C-Reactive Protein; Calcium; Cohort Studies; Coronary Angiography; Coronary Artery Disease; Cross-Sectional Studies; Diabetes Complications; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Risk Factors; Young Adult

Left ventricular hypertrophy (LVH) is a strong predictor of cardiovascular disease and is common among patients with type 2 diabetes. However, no systematic screening for LVH is currently recommended for patients with type 2 diabetes. The purpose of this study was to determine whether NT-proBNP was superior to 12-lead electrocardiography (ECG) for detection of LVH in patients with type 2 diabetes.. Prospective cross-sectional study comparing diagnostic accuracy of ECG and NT-proBNP for the detection of LVH among patients with type 2 diabetes. Inclusion criteria included having been diagnosed for > 5 years and/or on treatment for type 2 diabetes; patients with Stage 3/4 chronic kidney disease and known cardiovascular disease were excluded. ECG LVH was defined as either the Sokolow-Lyon or Cornell voltage criteria. NT-proBNP level was measured using the Roche Diagnostics Elecsys assay. Left ventricular mass was assessed from echocardiography. Receiver operating characteristic curve analysis was carried out and area under the curve (AUC) was calculated.. 294 patients with type 2 diabetes were recruited, mean age 58 (SD 11) years, BP 134/81 ± 18/11 mmHg, HbA 1c 7.3 ± 1.5%. LVH was present in 164 patients (56%). In a logistic regression model age, gender, BMI and a history of hypertension were important determinants of LVH (p < 0.05). Only 5 patients with LVH were detected by either ECG voltage criteria. The AUC for NT-proBNP in detecting LVH was 0.68.. LVH was highly prevalent in asymptomatic patients with type 2 diabetes. ECG was an inadequate test to identify LVH and while NT-proBNP was superior to ECG it remained unsuitable for detecting LVH. Thus, there remains a need for a screening tool to detect LVH in primary care patients with type 2 diabetes to enhance risk stratification and management.

Topics: Cross-Sectional Studies; Diabetes Mellitus, Type 2; Electrocardiography; Female; Humans; Hypertrophy, Left Ventricular; Male; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies

Patients with diabetes mellitus have a substantially increased risk of developing cardiovascular disease. However, the absolute risk greatly varies not only among patients, but the risk profile for an individual patient may also change over time. We investigated the prognostic role of repetitive measurements of Glycated haemoglobin A(1c) (HbA(1c) ) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients with longstanding diabetes.. For this prospective, observational study data from 544 consecutive patients were collected between 2005 and 2008. HbA(1c) and NT-proBNP were measured at baseline and after 1 year. The median observation period was 40 months. Endpoints were all-cause mortality, cardiac, cardiovascular and all-cause hospitalizations.. N-terminal pro-B-type natriuretic peptide concentrations significantly increased from 230 ± 385 to 280 ± 449 pg mL(-1) (P < 0·001); during the same time, HbA(1c) significantly decreased from 7·6 ± 1·5 to 7·3 ± 1·2 (P < 0·001). NT-proBNP was the best baseline predictor in a Cox regression model consisting of NT-proBNP, HbA(1c) , age, gender and duration of diabetes for all endpoints (P < 0·001). NT-proBNP at follow-up was the best predictor for the remaining period (P < 0·001, all endpoints). HbA(1c) at baseline and follow-up was predictive for all-cause hospitalizations (P = 0·005 both). In a third model that investigated the plasticity of both markers, changes in HbA(1c) concentration had no predictive value, but a change of NT-proBNP concentration was highly predictive (P = 0·025 all-cause mortality, P < 0·001 all other endpoints).. N-terminal pro-B-type natriuretic peptide and HbA(1c) concentrations significantly diverged over a 1-year period. NT-proBNP was the most potent predictor of outcome at baseline and follow-up, and changes in NT-proBNP concentrations were linked to an altered risk profile, unlike changes in HbA(1c) levels.

Topics: Aged; Biomarkers; Cardiovascular Diseases; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Prospective Studies; Regression Analysis; Risk Factors

This study tested the hypothesis that experimental prediabetes can elicit structural remodelling in the left ventricle (LV). Left ventricles isolated from 8-week-old male Goto-Kakizaki (GK) rats and age-matched male Wistar control rats were used to assess remodelling changes and underlying transforming growth factor β1 (TGFβ1) activity, prohypertrophic Akt-p70S6K1 signalling and gene expression profile of the extracellular matrix (ECM) using histological, immunohistochemical, immunoblotting and quantitative gene expression analyses. Prediabetes in GK rats was confirmed by impaired glucose tolerance and modestly elevated fasting blood glucose. Left ventricle remodelling in the GK rat presented with marked hypertrophy of cardiomyocytes and increased ECM deposition that together translated into increased heart size in the absence of ultrastructural changes or fibre disarray. Molecular derangements underlying this phenotype included recapitulation of the fetal gene phenotype markers B-type natriuretic peptide and α-skeletal muscle actin, activation of the Akt-p70S6K1 pathway and altered gene expression profile of key components (collagen 1α and fibronectin) and modulators of the ECM (matrix metalloproteinases 2 and 9 and connective tissue growth factor). These changes were correlated with parallel findings of increased TGFβ1 transcription and activation in the LV and elevated active TGFβ1 in plasma of GK rats compared with control animals (Student's t test, P < 0.05 versus age-matched Wistar control animals for all parameters). This is the first report to describe LV structural remodelling in experimental prediabetes. The results suggest that ventricular decompensation pathognomonic of advanced diabetic cardiomyopathy may have possible origins in profibrotic and prohypertrophic mechanisms triggered before the onset of type 2 diabetes mellitus.

Topics: Animals; Cardiomegaly; Diabetes Mellitus, Type 2; Extracellular Matrix Proteins; Heart Ventricles; Male; Natriuretic Peptide, Brain; Prediabetic State; Proto-Oncogene Proteins c-akt; Rats; Rats, Inbred Strains; Rats, Wistar; Ribosomal Protein S6 Kinases, 70-kDa; Signal Transduction; Transforming Growth Factor beta1; Ventricular Remodeling

Plasma osteoprotegerin (P-OPG) is an independent predictor of cardiovascular disease in diabetic and other populations. OPG is a bone-related glycopeptide produced by vascular smooth muscle cells and increased P-OPG may reflect arterial damage. We investigated the correlation between P-OPG and coronary artery disease (CAD) in asymptomatic type 2 diabetic patients with microalbuminuria.. P-OPG was measured in 200 asymptomatic diabetic patients without known cardiac disease. Patients with P-NT-proBNP >45.2 ng/l and/or coronary calcium score (CCS) ≥400 were stratified as high risk of CAD (n = 133), and all other patients as low risk patients (n = 67). High risk patients were examined by myocardial perfusion imaging (MPI; n = 109), and/or CT-angiography (n = 20), and/or coronary angiography (CAG; n = 86). Significant CAD was defined by presence of significant myocardial perfusion defects at MPI and/or >70% coronary artery stenosis at CAG.. Significant CAD was demonstrated in 70 of the high risk patients and of these 23 patients had >70% coronary artery stenosis at CAG. Among high risk patients, increased P-OPG was an independent predictor of significant CAD (adjusted odds ratio [CI] 3.11 [1.01-19.54] and 3.03 [1.00-9.18] for second and third tertile vs.first tertile P-OPG, respectively) and remained so after adjustments for NT-proBNP and CCS. High P-OPG was also associated with presence of >70% coronary artery stenosis(adjusted odds ratio 14.20 [1.35-148.92] for third vs. first tertile P-OPG), and 91% of patients with low (first tertile) P-OPG did not have >70% coronary artery stenosis.. Elevated P-OPG is an independent predictor of the presence of CAD in asymptomatic type 2 diabetic patients with microalbuminuria.

Topics: Adult; Aged; Albuminuria; Biomarkers; Calcium; Comorbidity; Coronary Angiography; Coronary Artery Disease; Coronary Vessels; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Osteoprotegerin; Peptide Fragments; Predictive Value of Tests; Retrospective Studies; Risk Factors

Intensive multifactorial treatment aimed at cardiovascular (CV) risk factor reduction in type 2 diabetic patients with microalbuminuria can diminish fatal and non-fatal CV. Plasma N-terminal (NT)-proBNP predicts CV mortality in diabetic patients but the utility of P-NT-proBNP in screening for atherosclerosis is unclear. We examined the interrelationship between P-NT-proBNP, presence of atherosclerosis and/or vascular dysfunction in the coronary, carotid and peripheral arteries in asymptomatic type 2 diabetic patients with microalbuminuria that received intensive multifactorial treatment.. P-NT-proBNP was measured in 200 asymptomatic type 2 patients without known cardiac disease that received intensive multifactorial treatment for CV risk reduction. Patients were examined for coronary, carotid and peripheral atherosclerosis, as defined by coronary calcium score≥400, carotid intima-media thickness (CIMT)>0.90 mm, ankle-brachial index<0.90, and/or toe-brachial index<0.64, respectively. Carotid artery compliance was also determined and the reactive hyperaemia index (RHI) measured by peripheral artery tonometry was used as a surrogate for endothelial function.P-NT-proBNP was associated with atherosclerosis in the unadjusted analysis, but not after adjustment for conventional risk factors. P-NT-proBNP was not associated with vascular dysfunction. The prevalence of atherosclerosis in the coronary, carotid and peripheral arteries was 35%, 10% and 21% of all patients, respectively. In total 49% had atherosclerosis in one territory and 15.6% and 1.0% in two and three territories. Low RHI was an independent predictor of coronary atherosclerosis (odds ratio [CI], 2.60 [1.15-5.88] and systolic blood pressure was the only independent determinant of CIMT (0.02 mm increase in CIMT per 10 mmHg increase in systolic blood pressure [p=0.003]).. Half of asymptomatic patients with type 2 diabetes mellitus and microalbuminuria had significant atherosclerosis in at least one vascular territory despite receiving intensive multifactorial treatment for CV risk reduction. Coronary atherosclerosis was most prevalent, whereas carotid disease was more rarely observed. RHI but not plasma NT-proBNP was predictive of coronary atherosclerosis.

Topics: Aged; Albuminuria; Ankle Brachial Index; Biomarkers; Carotid Arteries; Carotid Intima-Media Thickness; Comorbidity; Coronary Artery Disease; Diabetes Mellitus, Type 2; Female; Humans; Hyperemia; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Risk Factors

In patients with chronic kidney disease (CKD), as in other populations, elevations in cardiac biomarker levels predict increased risk of cardiovascular events. We examined the value of troponin T (TnT) and N-terminal pro-brain natriuretic peptide (NT-pro-BNP) in assessing the risk of developing end-stage renal disease (ESRD) in diabetic patients with CKD.. Prospective cohort study nested within a randomized clinical trial.. Patients with type 2 diabetes, CKD (estimated glomerular filtration rate [eGFR], 20-60 mL/min/1.73 m(2)), and anemia enrolled in TREAT (Trial to Reduce Cardiovascular Events With Aranesp Therapy).. Serum levels of the cardiac biomarkers TnT and NT-pro-BNP.. Incidence of ESRD and the composite of death or ESRD.. We measured TnT and NT-pro-BNP in baseline serum samples from the first 1,000 patients enrolled in TREAT. The relationship of these cardiac biomarker levels to the development of ESRD and death or ESRD was analyzed in multivariable regression models.. Detectable TnT (≥0.01 ng/mL) was present in 45% of participants, and median NT-pro-BNP level was elevated at 605 pg/mL. Higher levels of both cardiac biomarkers were associated independently with higher rates of ESRD, as well as death or ESRD, and remained prognostically important after adjustment for eGFR, proteinuria, and other known predictors of CKD progression. The addition of cardiac biomarkers to a multivariable model for prediction of ESRD improved discrimination of those with and without an event by 16.9% (95% CI, 6.3%-27.4%).. Observational study in a clinical trial cohort; results require validation.. In ambulatory patients with type 2 diabetes, anemia, and CKD, TnT and NT-pro-BNP levels frequently are elevated. These cardiac-derived biomarkers enhance prediction of ESRD beyond established risk factors. Measurement of TnT and NT-pro-BNP may improve the identification of patients with CKD who are likely to require renal replacement therapy, supporting a link between cardiac injury and the development of ESRD.

Topics: Aged; Anemia; Biomarkers; Chronic Disease; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Female; Humans; Kidney Diseases; Kidney Failure, Chronic; Male; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Risk Factors; Troponin T

Laboratory tests contribute to patient length of stay in the emergency department. Therefore, rapid tests performed at the bedside (POCT or point of care testing) are attractive because they allow the emergency physician to obtain immediate biological, diagnostic and/or prognostic data. Userfriendly and with validated analytical performance, POCT have the potential to reduce laboratory time, patient length of stay and time to treatment or disposition. The expected benefit from POCT implementation will depend on the type of patients involved (inpatient or outpatient), their clinical condition and their overall care. Furthermore, logistical and economic implications should also be taken into account.

Topics: Acute Coronary Syndrome; Antifibrinolytic Agents; Biomarkers; Critical Care; Diabetes Complications; Diabetes Mellitus, Type 2; Emergency Service, Hospital; Fibrin Fibrinogen Degradation Products; Heart Failure; Hospital Costs; Humans; Length of Stay; Natriuretic Peptide, Brain; Point-of-Care Systems; Predictive Value of Tests; Prognosis; Pulmonary Disease, Chronic Obstructive; Pulmonary Embolism; Risk Assessment; Sensitivity and Specificity; Switzerland; Treatment Outcome; Troponin

Topics: Anemia; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Female; Humans; Kidney Diseases; Kidney Failure, Chronic; Male; Natriuretic Peptide, Brain; Peptide Fragments; Troponin T

Genetic and epidemiological evidence suggests an inverse association between B-type natriuretic peptide (BNP) levels in blood and risk of type 2 diabetes (T2D), but the prospective association of BNP with T2D is uncertain, and it is unclear whether the association is confounded.. We analysed the association between levels of the N-terminal fragment of pro-BNP (NT-pro-BNP) in blood and risk of incident T2D in a prospective case-cohort study and genotyped the variant rs198389 within the BNP locus in three T2D case-control studies. We combined our results with existing data in a meta-analysis of 11 case-control studies. Using a Mendelian randomization approach, we compared the observed association between rs198389 and T2D to that expected from the NT-pro-BNP level to T2D association and the NT-pro-BNP difference per C allele of rs198389. In participants of our case-cohort study who were free of T2D and cardiovascular disease at baseline, we observed a 21% (95% CI 3%-36%) decreased risk of incident T2D per one standard deviation (SD) higher log-transformed NT-pro-BNP levels in analysis adjusted for age, sex, body mass index, systolic blood pressure, smoking, family history of T2D, history of hypertension, and levels of triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol. The association between rs198389 and T2D observed in case-control studies (odds ratio = 0.94 per C allele, 95% CI 0.91-0.97) was similar to that expected (0.96, 0.93-0.98) based on the pooled estimate for the log-NT-pro-BNP level to T2D association derived from a meta-analysis of our study and published data (hazard ratio = 0.82 per SD, 0.74-0.90) and the difference in NT-pro-BNP levels (0.22 SD, 0.15-0.29) per C allele of rs198389. No significant associations were observed between the rs198389 genotype and potential confounders.. Our results provide evidence for a potential causal role of the BNP system in the aetiology of T2D. Further studies are needed to investigate the mechanisms underlying this association and possibilities for preventive interventions. Please see later in the article for the Editors' Summary.

Topics: Aged; Alleles; Case-Control Studies; Cohort Studies; Diabetes Mellitus, Type 2; Female; Genetic Variation; Genotype; Humans; Male; Meta-Analysis as Topic; Middle Aged; Natriuretic Peptide, Brain; Prospective Studies; Risk Assessment

Soluble ST2, a member of the of the Toll/IL-1 superfamily, is a novel biomarker with exceptional predictive value in heart failure and myocardial infarction- related mortality as well as in acute dyspneic states. Soluble ST2 is considered a decoy receptor of IL 33 that blocks the protective effects of the cytokine in atherosclerosis and cardiac remodeling. In the present study we investigated the differences in the levels of soluble ST2, BNP and hs-CRP between healthy controls and patients with type 2 diabetes with and without left ventricular diastolic dysfunction. A secondary aim was to investigate correlations between sST2 and other biomarkers of type 2 diabetes, such as HbA1c.. 158 volunteers were recruited and underwent a complete Doppler-echocardiographic evaluation of both systolic & diastolic cardiac function. All subjects with ejection fraction<50% were excluded. The study population was divided in 4 groups as follows: A: 42 healthy controls, B: 18 subjects without diabetes with LVDD, C: 48 patients with type 2 diabetes without LVDD & D: 50 patients with type 2 diabetes & LVDD. ELISA technique was performed to measure sST2 levels. Statistical analysis was performed with Kruskal-Wallis & Mann-Whitney test (continuous variables), chi squared & Fischer exact test (discrete variables), Spearman coefficient (univariate analysis) and step-wise backward method (multivariate analysis).. Patients with type 2 diabetes with (p<0.001) or without LVDD (p=0.007) had higher serum ST2 levels compared to healthy controls, state found also for hs-CRP levels but not for the corresponding BNP levels (p=0.213 & p=0.207 respectively). Patients with type 2 diabetes & LVDD had higher serum ST2 in relation to diabetic patients without LVDD (p=0.001). In multivariate analysis HbA1c positively and independently correlated with sST2 levels in both groups of patients with type 2 diabetes.. Patients with type 2 diabetes exhibit higher sST2 levels compared to healthy controls. The presence of LVDD in patients with type 2 diabetes is associated with even higher sST2 levels. A significant correlation between glycemic control and sST2 levels was also revealed.

Topics: Aged; Biomarkers; C-Reactive Protein; Case-Control Studies; Chi-Square Distribution; Diabetes Mellitus, Type 2; Echocardiography, Doppler; Female; Glycated Hemoglobin; Greece; Humans; Interleukin-1 Receptor-Like 1 Protein; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Receptors, Cell Surface; Risk Assessment; Risk Factors; Stroke Volume; Up-Regulation; Ventricular Dysfunction, Left; Ventricular Function, Left

Sleep-disordered breathing (SDB), especially sleep apnea-hypopnea syndrome, is often observed in patients with type 2 diabetes mellitus; but there are only a few studies on SDB in Japanese diabetic subjects. We investigated the prevalence of SDB in diabetic patients; associations between severity of sleep apnea (SA) and clinical factors, visceral fat, and adiponectin; and associations between type of SA and clinical factors. In the present study, 40 Japanese diabetic patients underwent overnight cardiorespiratory monitoring, and night and morning measurements of serum adiponectin concentrations. Sleep apnea was detected in Japanese diabetic patients at a high prevalence (77.5%). The following variables were associated with SDB: age, body mass index, estimated visceral fat area, and nocturnal reduction in serum adiponectin concentrations. The prevalence of central sleep apnea (CSA, >or=5/h) was 32.3% among diabetic SDB patients. Diabetic SDB patients with CSA had higher hemoglobin, increased intima-media thickness, and higher plasma brain natriuretic peptide levels than those without CSA (<5/h). In conclusion, our study demonstrated a high prevalence of SDB in Japanese diabetic patients, which correlated with visceral fat area and adiponectin. A high frequency of CSA was noted in diabetic SDB patients, together with high hemoglobin, high brain natriuretic peptide, and increased intima-media thickness. The present results of prevalence of SDB may be relevant to the higher incidence of cardiovascular disease in diabetic patients, which need to be clarified in future studies.

Topics: Adiponectin; Adipose Tissue; Adult; Aged; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Japan; Male; Middle Aged; Natriuretic Peptide, Brain; Prevalence; Sleep Apnea, Central; Statistics, Nonparametric; Tunica Intima; Ultrasonography

: The aim of this study was to determine serum NT-proBNP and plasma Hcy levels and to explore the relationship between serum NT-proBNP and plasma Hcy levels in type 2 diabetic patients with and without asymptomatic LVDD.. : NT-proBNP and Hcy levels were measured 31 patients with type 2 diabetes mellitus. According to echocardiographic data, diabetic patients were divided into two groups: normal LV function or LV diastolic dysfunction.. : Serum NT-proBNP levels in diabetic patients with LVDD were significantly higher than in diabetic patients with normal LV function and controls. The area under the receiver-operating characteristic (ROC) curve for NT-proBNP to separate normal vs. diastolic dysfunction was 0.96 in type 2 diabetic patients. Plasma Hcy levels were significantly higher in both diabetic groups than in controls. Positive correlation was noted between NT-proBNP and Hcy levels in diabetic patients with LVDD (r=0.881, p=0.0001).. : The correlation between elevated NT-proBNP and Hcy levels in diabetic patients with LVDD suggest an association between homocysteinemia and increased NT-proBNP secretion. Our data indicate that NT-proBNP may be a simple screening tool to select diabetic patients with LVDD requiring further examination with echocardiography.

Topics: Blood Pressure; Creatinine; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diastole; Echocardiography; Echocardiography, Transesophageal; Female; Homocysteine; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Ventricular Dysfunction, Left; Ventricular Function, Left

The aims of this study were to estimate the prevalence of left ventricular systolic (LVSD) and diastolic (LVDD) dysfunction, and to test if BNP and urinary albumin excretion rate (AER) are related to LVSD, LVD and left ventricular mass (LVM) in asymptomatic type 2 diabetes patients.. Presence of LVSD, LVDD and LVM, determined with echocardiography, was related to levels of BNP and AER in 153 consecutive asymptomatic patients with type 2 diabetes.. LVSD was present in 6.1% of patients whereas 49% (29% mild, 19% moderate and 0.7% severe) had LVDD and 9.4% had left ventricular hypertrophy. Increasing age (P < 0.0001) was the only independent variable related to mild LVDD whereas increasing BNP (P = 0.01), systolic blood pressure (P = 0.01), age (P = 0.003) and female gender (P = 0.04) were independent determinants of moderate to severe LVDD. AER (P = 0.003), age (P = 0.01) and male gender (P = 0.006) were directly and independently related to LVM.. About half of asymptomatic type 2 diabetes patients have LVDD. Of those, more than one third display moderate LVDD pattern paralleled by increases in BNP, suggesting markedly increased risk of heart failure, especially in females, whereas AER and male sex are related to LVM.

Topics: Adult; Albuminuria; Blood Pressure; Body Mass Index; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diastole; Echocardiography; Female; Heart Ventricles; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Organ Size; Ventricular Dysfunction, Left

The association between BMI and low levels of B-type natriuretic peptide (BNP), a marker of heart failure, has been demonstrated in a large population-based cohort. We examined the effects of obesity on BNP levels in patients with diabetes that are often associated with obesity and a higher risk for heart failure.. Plasma BNP levels, BMI, and cardiac function parameters were measured in 608 patients with type 2 diabetes. A computed tomography scan was performed to measure abdominal fat.. In multivariable regression analyses adjusted for age, sex, systolic blood pressure, pulse rate, serum creatinine, asynergy, left atrial dimension, percent fractional shortening, and left ventricular mass, there was an inverse relationship between BMI and BNP (p<0.001). Obese individuals with 25

Topics: Aged; Body Mass Index; Diabetes Mellitus, Type 2; Female; Humans; Intra-Abdominal Fat; Male; Middle Aged; Natriuretic Peptide, Brain

To study the distribution of adiponectin isoforms in a group of very old patients.. Cross-sectional.. Geriatric ambulatory clinic of the Department of Medicine at Policlinico "Tor Vergata.". One hundred eight elderly adults (mean age 85.0+/-3.2) with or without a history of a previous myocardial infarction as proof of established coronary artery disease (CAD) at least 3 months before entry into the study. Accordingly, subjects were divided into CAD positive (CAD+, n=50) and CAD negative (CAD-, n=58).. Assessment of adiponectin isoforms along with metabolic, lipid, and inflammatory profiles.. CAD+ subjects had significantly higher levels of total adiponectin (Tot-Ad) and low-molecular-weight adiponectin (LMW-Ad) than CAD- subjects (P=.008 for both). LMW-Ad and high-sensitivity C-reactive protein were positively correlated, even after adjustment for waist circumference, sex, glomerular filtration rate, and presence of diabetes mellitus (correlation coefficient (r)=0.25, P=.05). This association was not confirmed when CAD+ subjects were analyzed alone. A positive association was found in CAD+ subjects between brain natriuretic peptide (BNP), high-molecular-weight adiponectin (HMW-Ad), and Tot-Ad (r=0.798 and r=0.795, P<.001 for all) but not LMW-Ad.. Distribution of adiponectin isoforms differed in populations of elderly subjects according to the presence of coronary atherosclerosis. The data support the hypothesis for a protective role of LMW-Ad during aging, although additional studies are needed to definitively clarify whether LMW-Ad plays a protective role in older people with a history of CAD.

Topics: Adiponectin; Aged, 80 and over; Aging; Analysis of Variance; Body Mass Index; C-Reactive Protein; Case-Control Studies; Chi-Square Distribution; Coronary Artery Disease; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Female; Glomerular Filtration Rate; Humans; Male; Molecular Weight; Natriuretic Peptide, Brain; Protein Isoforms; Rome; Sex Characteristics; Waist Circumference

This study evaluated the relationship between natriuretic peptide levels and a wide range of echocardiography parameters in a population of thirty-three patients with poorly regulated type 2 diabetes, and no known heart failure. Natriuretic peptides brain natriuretic peptide (BNP) and N-terminal prohormone BNP (NT-proBNP) were measured. Transthoracic echocardiography was performed and cardiac volumes and ejection fraction were measured. Doppler and tissue Doppler were measured and diastolic function was stratified according to recent guidelines. Very few echocardiography parameters were correlated with BNP or NT-proBNP levels. However, left atrial end-systolic volume indexed for body surface area was correlated with natural logarithm (ln) BNP and ln NT-proBNP (r=0.62 and r=0.60; P<0.05). There were significant differences in ln BNP and ln NT-proBNP levels between those with normal and those with abnormal diastolic function (1.4 vs 3.1; P<0.001 and 3.4 vs 5.8; P<0.001). This study showed that very few echocardiography parameters were correlated with BNP or NT-proBNP levels in patients with poorly regulated type 2 diabetes, which in part contradicts previous studies in other diabetic populations. The exception was left atrial end-systolic volume that showed a moderate correlation with BNP or NT-proBNP levels. There were significant differences in BNP and NT-proBNP levels between the group with normal left ventricular diastolic function and the group with abnormal diastolic function.

Topics: Aged; Atrial Function, Left; Biomarkers; Blood Glucose; Diabetes Mellitus, Type 2; Echocardiography, Doppler, Pulsed; Female; Glycated Hemoglobin; Heart Failure; Humans; Hypoglycemic Agents; Male; Middle Aged; Myocardial Contraction; Natriuretic Peptide, Brain; Peptide Fragments; Pilot Projects; Stroke Volume; Treatment Outcome; Ventricular Function, Left

Higher plasma B-type natriuretic peptide (BNP) in a non-heart failure (HF) range predicts HF and cardiovascular disease (CVD) mortality in the general population. Heart failure is highly prevalent in type 2 diabetes mellitus (T2DM), but associations of BNP to left ventricular (LV) mass and function in individuals with a different glucose status have not been compared. We therefore aimed to explore (i) the association of BNP levels in a non-HF range with structural and functional markers of LV function, and (ii) possible effect modification by glucose tolerance categories.. Linear regression analyses were performed to investigate associations of BNP with 2D echocardiographic measures of LV mass index, LV systolic function, and markers of LV diastolic function in a population-based study of men and women with normal glucose metabolism (NGM, n = 197), impaired glucose metabolism (IGM, n = 128), or T2DM (n = 204). Patients were aged between 50 and 87 years, had BNP levels below 50 pmol/L, and no LV wall motion abnormalities. B-type natriuretic peptide levels ranged from 0.4 to 46.1 pmol/L, the median was 4.2 pmol/L. Higher BNP was significantly associated with increased LV mass and deteriorated LV diastolic function, but not with LV systolic function. B-type natriuretic peptide was more strongly associated with LV diastolic function in T2DM compared with NGM and IGM.. B-type natriuretic peptide was associated with LV mass and markers of LV diastolic function, and the association of BNP with the latter appeared to be particularly strong in individuals with T2DM. This implies that the presence or absence of T2DM should be taken into account if BNP levels are used to assess CVD risk.

Topics: Aged; Aged, 80 and over; Biomarkers; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Diastole; Disease Progression; Female; Heart Failure; Humans; Immunoradiometric Assay; Male; Middle Aged; Natriuretic Peptide, Brain; Prevalence; Prognosis; Retrospective Studies; Ventricular Dysfunction, Left; Ventricular Function, Left

Urotensin II (UII) exerts multiple effects on the cardiovascular system, acts as a diabetogenic agent, and may also contribute to the development of the metabolic syndrome (MetS). The aim of this study was to determine circulating UII in patients with type 2 diabetes mellitus (T2DM) and its relationship with MetS. A total of 360 consecutive patients with T2DM were included. MetS presence/absence (MetS [+]/[-]) was defined according to American Heart Association/National Heart, Lung and Blood Institute criteria. Plasma concentrations of UII were determined by radioimmunoassay. UII levels were significantly higher in MetS (+) than in MetS (-) T2DM patients (0.97 pg/mL [0.93-1.01], n=294 vs 0.82 pg/mL [0.75-0.88] pg/mL, n=66, respectively; P<.001). Multiple logistic regression analysis showed that UII was significantly associated with MetS (+) (odds ratio, 6.41 [95% confidence interval, 1.21-16.04]; P=.02). UII plasma concentrations are significantly higher in T2DM patients presenting with MetS. Therefore, circulating UII may participate in the worsening course of some T2DM patients and may provide novel therapeutic perspectives.

Topics: Aged; Atrial Natriuretic Factor; Biomarkers; Diabetes Mellitus, Type 2; Female; Humans; Logistic Models; Male; Metabolic Syndrome; Middle Aged; Natriuretic Peptide, Brain; Phenotype; Protein Precursors; Retrospective Studies; Urotensins

In the early identification of cardiovascular risk, it is essential to establish a biological marker for cardiac complications that is comparable to albuminuria for nephropathy. We tested the hypothesis that N-terminal pro-brain natriuretic peptide (NT-proBNP) might be a marker for silent myocardial ischaemia in diabetes.. In forty consecutively recruited subjects without evident coronary artery disease, serum NT-proBNP was measured together with multi-slice computed tomography. With patients suspected of having significant coronary artery stenosis by multi-slice computed tomography, coronary angiography was performed. Silent myocardial ischaemia was defined as the presence of significant coronary artery stenosis with more than 50% luminal narrowing by angiography.. Thirteen patients (32.5%) had silent myocardial ischaemia. NT-proBNP levels were significantly higher in these patients (181.1 ± 43.8 versus 55.2 ± 9.7 pg/mL, p < 0.005) but HbA(1c), lipid profiles, and creatinine were similar in the two groups. Moreover, log NT-proBNP was identified as an independent predictor of silent myocardial ischaemia (R(2) = 0.502, p < 0.05) after adjustment for HbA(1c), creatinine, albuminuria, hypertension, hyperlipidaemia, or smoking. After stratifying patients by NT-proBNP, the upper tertile compared to the lowest tertile was significantly associated with silent myocardial ischaemia (odds ratio: 26.7, p < 0.05). Receiver operation characteristics analysis with a cut-off value of 52 pg/mL showed 92% sensitivity and 75% specificity for predicting silent myocardial ischaemia (positive predictive value 64.7%, negative predictive value 94.3%).. The outstandingly high negative predictive value of NT-proBNP enables us to focus on diabetic patients with occult coronary disease, independently of microalbuminuria.

Topics: Aged; Albuminuria; Biomarkers; Coronary Angiography; Coronary Artery Disease; Coronary Stenosis; Creatinine; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Glycated Hemoglobin; Humans; Hyperlipidemias; Hypertension; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Risk Factors

The aim of the present study was to verify whether BNP might detect pre-clinical diastolic dysfunction (LVDD) in type-2 diabetic patients.. One-hundred and twenty-seven consecutive outpatients with type-2 diabetes mellitus were enrolled into the study. Subjects with overt heart failure or NYHA class > 1, history of coronary artery disease, severe valvulopathy or chronic atrial fibrillation were excluded from the study. All patients underwent clinical evaluation, laboratory assessment of brain natriuretic peptide (BNP) and echocardiographic examination.. No patients showed systolic impairment of left ventricular function, whereas diastolic dysfunction was detected in 53 (42%) cases (all impaired relaxation). Median BNP was 27 pg/ml without any significant difference between 76 patients with normal left ventricular function and 53 with diastolic dysfunction; in 54 (43%) patients showing HBA1C≥8 (uncontrolled diabetes) normal function was found in 32 and diastolic dysfunction in 22, with a significant difference of BNP at multivariate analysis (OR = 1.02, 95%CI = 1.05-1.09, p = 0.003). In uncontrolled diabetic cohort, BNP was a strong predictor for LVDD (OR = 2.7, 95%CI = 1.3-5.6, p = 0.006) along with the duration of diabetes (OR = 1.6, 95%CI = 1.1-2.9, p = 0.046). BNP > 25 pg/ml was a cut-off value with high accuracy to detect a LVDD.. Early screening of high-risk patients for diabetic cardiomyopathy development might be useful to better control glycemic profile in order to reduce heart disease progression or even to reverse it. BNP could be a cheap, easy and useful tool to screen those ones with preclinical ventricular diastolic dysfunction in a subset of patients particularly prone to develop cardiovascular complications, like uncontrolled diabetic patients.

Topics: Adult; Aged; Biomarkers; Chi-Square Distribution; Diabetes Complications; Diabetes Mellitus, Type 2; Diastole; Early Diagnosis; Echocardiography, Doppler, Color; Echocardiography, Doppler, Pulsed; Female; Glycated Hemoglobin; Humans; Italy; Logistic Models; Male; Middle Aged; Natriuretic Peptide, Brain; Odds Ratio; Predictive Value of Tests; Risk Assessment; Risk Factors; Ventricular Dysfunction, Left; Ventricular Function, Left

This study aimed for a comprehensive evaluation of major depressive disorder (MDD) in stable coronary heart disease (CHD) patients, excluding all other potential psychiatric comorbidities, and including associations with cardiac biomarkers such as C-reactive protein (CRP), troponin T (TnT), and amino-terminal pro-B-type brain natriuretic peptide (NT-proBNP).. Cross-sectional study of a consecutive series of 72 stable CHD outpatients (n=30 with MDD, n=42 with no psychiatric disorder). Psychiatric diagnoses were established by using the Structured Clinical Interview for DSM-IV (SCID), and psychiatric assessment was performed on Axis I, Axis III, Axis IV, and Axis V. Regression analyses were performed including CRP, TnT, and NT-proBNP as dependent variables, and MDD, demographics, and comorbid medical conditions as independent variables.. Stepwise multiple regression analyses showed a significant association between MDD and CRP (beta=0.262, P=.02), excluding all other demographic and medical variables from the models, except age (beta=0.266, P=.02). In addition, the results described a significant relationship between type II diabetes mellitus and TnT (beta=0.267, P=.02), and age and NT-proBNP levels (beta=0.374, P=.001).. Major depressive disorder was associated with elevated CRP levels in a consecutive series of stable CHD patients.

Topics: Aged; Biomarkers; C-Reactive Protein; Comorbidity; Coronary Disease; Cross-Sectional Studies; Depressive Disorder, Major; Diabetes Mellitus, Type 2; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Troponin

Sleep-disordered breathing (SDB) is often encountered in morbid obesity (MO) in conjunction with insulin resistance (IR) and several cardio-vascular risk factors. Aminoterminal pro-brain natriuretic peptide (NT-proBNP) is a promising marker for left ventricular dysfunction (LVD) in MO. The aim of this study was to look for possible correlations between SDB, IR, heart structure and function indexes and NT-proBNP levels in MO female subjects.. Cross-sectional study involving 110 MO (44.5+/-0.7 kg m(-2)) apparently healthy, young (37.8+/-1.0 y.o.) female patients. NT-proBNP was measured using an ELISA kit (Roche). Echo-cardiograms were performed to quantify left ventricular ejection fraction values (LVEF), cardiac output (CO), left ventricular mass (LVM), left atria size (LA) and left ventricular filling pressures (the E/Em ratio). The Berlin Questionnaire (BQ) was used to assess the risk of SDB. IR and sensitivity were assessed using the HOMA index and adiponectin measurements, respectively.. All patients had a normal LVEF (>50%). Hypertension and Type 2 diabetes mellitus prevalences were 34.5 and 4.5% (respectively). Log-transformed NT-proBNP levels correlated with BQ categories (P<0.0005), creatinine (P<0.001), age (P<0.05), LVM (P<0.001), CO (P<0.001), LA (P<0.0005) and E/Em (P<0.01). NT-proBNP levels, LVD and LVM increased significantly along with BQ scores (P<0.0001). Stepwise multiple regression analysis identified BQ and log-transformed HOMA as independent variables predicting as much as 48.0% of log-transformed NT-proBNP's variability (dependent variable).. NT-proBNP levels are independently predicted by SDB and IR in asymptomatic MO women. Additionally, SDB worsens along with LVH and diastolic dysfunction. Larger prospective studies are warranted.

Topics: Adult; Biomarkers; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Echocardiography; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Insulin Resistance; Linear Models; Natriuretic Peptide, Brain; Obesity, Morbid; Peptide Fragments; Predictive Value of Tests; Prevalence; Risk Factors; Sleep Apnea Syndromes

Multiple coronary artery occlusive disease (multiple CAOD) is the most fatal and frequently observed coronary artery disease in type 2 diabetes patients, but no simple, non-invasive screening tool is available yet. The aim of this study is to evaluate the arterial stiffness in type 2 diabetes patients using brachial-ankle pulse wave velocity (baPWV), to demonstrate the correlation between arterial stiffness and multiple CAOD, and to suggest the cutoff point of baPWV for predicting multiple CAOD in Korean type 2 diabetes patients. One hundred and eighty-one diabetes and 262 non-diabetes patients were enrolled in the study. Routine anthropometric and serologic data were collected. baPWV was measured the day before coronary angiography, and the severity of CAOD was assessed with Gensini score after angiography. baPWV and Gensini score were significantly increased in diabetes patients and Gensini score had a positive correlation with baPWV. Subjects in the highest tertile of baPWV showed odds ratio of 3.06 for multiple CAOD compared to the lowest tertile. In ROC curve, baPWV at 1635 cm/s showed 73% sensitivity and 75% specificity with AUC 0.76 in diabetes patients in detecting multiple CAOD. Therefore, baPWV may be utilized a screening tool for predicting multiple CAOD, especially in type 2 diabetes patients.

Topics: Aged; Ankle; Ankle Brachial Index; Arterial Occlusive Diseases; Blood Pressure; C-Reactive Protein; Coronary Disease; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Humans; Korea; Male; Middle Aged; Natriuretic Peptide, Brain; Pulse; Sensitivity and Specificity

To determine whether plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, a marker for cardiac failure and potentially for the severity of coronary artery disease (CAD), predicts silent myocardial ischaemia (SMI) and silent CAD in asymptomatic high-risk diabetic patients.. Five hundred and seventeen asymptomatic diabetic patients with > or = 1 additional cardiovascular risk factor but without heart failure were prospectively screened between 1998 and 2008 for SMI, defined as an abnormal stress myocardial scintigraphy, and subsequently for significant (> 70%) angiographic CAD. The 323 patients with interpretable echocardiography and for whom NT-proBNP was measured were included in this analysis.. SMI was found in 108 (33.4%) patients, 39 of whom had CAD. NT-proBNP was higher in the patients with CAD than in the patients without CAD [45.0 (1-3199) vs. 20.0 (1-1640) pg/ml; P < 0.0001 median (range)], even after adjustment for confounding factors: age, gender, body mass index, glycated haemoglobin (HbA(1c)), retinopathy, nephropathy, hypertension, echocardiographic parameters (P < 0.05). NT-proBNP in the third tertile (> or = 38 pg/ml) predicted CAD with a sensitivity of 59% and a specificity of 67%. In a multiple logistic regression analysis including NT-proBNP > or = 38 pg/ml, age, body mass index, gender, HbA(1c), hypertension, retinopathy, nephropathy, peripheral occlusive arterial disease, left ventricular systolic dysfunction, dilatation and hypertrophy and Type 1 transmitral flow, NT-proBNP > or = 38 pg/ml was the only significant independent predictor of silent CAD [odds ratio (OR) 3.1 (95% confidence interval 1.3-7.6), P = 0.015].. NT-proBNP measurement helps to better define asymptomatic diabetic patients with an increased likelihood for CAD, independently of cardiac function and structure.

Topics: Biomarkers; Coronary Artery Disease; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Ultrasonography; Ventricular Dysfunction, Left

The aim of this study was to determine whether there are differences in echocardiographic findings or in the level of a biochemical marker (i.e. N-terminal probrain natriuretic peptide [NT-proBNP]) between controls and type-2 diabetic patients with or without ischemic heart disease. Echocardiography was used to assess left ventricular function and morphology. In addition, the plasma NT-proBNP concentration was measured. The prevalence of diastolic dysfunction was greater in diabetics without ischemic heart disease than in controls (88% vs. 74%, respectively; P< .001) and the NT-proBNP concentration was higher (350.6+/-197.8 vs. 281.7+/-190.4 fmol/mL; P< .001). Diabetics with ischemic heart disease had a higher NT-proBNP concentration than those without (720.4+/-278.1 vs. 350.6+/-197.8 fmol/mL, respectively; P< .001). An NT-proBNP concentration >490 fmol/mL had a sensitivity of 84% and a specificity of 75% for detecting ischemic heart disease in diabetics.

Topics: Aged; Diabetes Mellitus, Type 2; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Ultrasonography

To assess relations between severity of chronic cardiac failure (CCF) and a course of comorbid type 2 diabetes mellitus (DM).. Time course changes of cerebral natriuretic peptide (CNUP) were used as a criterion of CCF severity in 81 patients with mild and moderate CCF (NYHA functional class II-III), left ventricular ejection fraction (LVEF) < 45% and type 2 DM. Of them, two groups of 19 patients each were compiled--with the highest and lowest CNUP levels. Also, patients with a rising CNUP level and CCF FC (n = 5) and those with decreasing CNUP and FC improvement (n = 33) were analysed. The following parameters were studied at baseline and 6 months later: clinicofunctional status, glomerular filtration rate (GFR), neurohormonal profile (CNUP), noradrenalin and angiotensin II, the level of HbA1c, baseline and postprandial plasma glucose, serum insulin and C-peptide.. Insignificant changes in glycemia in low C-peptide were found in groups with mild CCF. In patients with high CNUP and CCF FC there was a positive correlation between high CNUP, noradrenalin and fasting glucose. With growing severity of CCF clinicofunctional status of the patients was deteriorating while levels of noradrenalin and angiotensin II tended to rise.. Moderate decompensation of CCF had no effect on the course of associated DM. More severe and long-term decompensation may be accompanied with noticeable changes in glycemia.

Topics: Aged; Angiotensin II; C-Peptide; Comorbidity; Diabetes Mellitus, Type 2; Female; Heart Failure; Humans; Insulin; Male; Middle Aged; Natriuretic Peptide, Brain; Norepinephrine; Retrospective Studies; Severity of Illness Index

Increased salt intake may induce hypertension, lead to cardiac hypertrophy, and exacerbate heart failure. When elderly patients develop heart failure, diastolic dysfunction is often observed, although the ejection fraction has decreased. Diabetes mellitus (DM) is an established risk factor for heart failure. However, little is known about the relationship between cardiac function and urinary sodium excretion (U-Na) in patients with DM.. We measured 24-hour U-Na; cardiac function was evaluated directly during coronary catheterization in type 2 DM (n = 46) or non-DM (n = 55) patients with preserved cardiac systolic function (ejection fraction > or = 60%). Cardiac diastolic and systolic function was evaluated as - dp/dt and + dp/dt, respectively.. The average of U-Na was 166.6 +/- 61.2 mEq/24 hour (mean +/- SD). In all patients, stepwise multivariate regression analysis revealed that - dp/dt had a negative correlation with serum B-type natriuretic peptide (BNP; beta = - 0.23, P = .021) and U-Na (beta = - 0.24, P = .013). On the other hand, + dp/dt negatively correlated with BNP (beta = - 0.30, P < .001), but did not relate to U-Na. In the DM-patients, stepwise multivariate regression analysis showed that - dp/dt still had a negative correlation with U-Na (beta = - 0.33, P = .025).. The results indicated that increased urinary sodium excretion is associated with an impairment of cardiac diastolic function, especially in patients with DM, suggesting that a reduction of salt intake may improve cardiac diastolic function.

Topics: Aged; Biomarkers; Cardiac Catheterization; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Diastole; Diet, Sodium-Restricted; Female; Humans; Male; Middle Aged; Natriuresis; Natriuretic Peptide, Brain; Regression Analysis; Risk Assessment; Risk Factors; Sodium; Sodium Chloride, Dietary; Systole; Ventricular Dysfunction, Left; Ventricular Function, Left; Ventricular Pressure

Cardiovascular autonomic neuropathy (CAN) is a complication of diabetes mellitus (DM) and has been regarded as a parameter associated with a poor outcome.. We investigated whether indices of cardiovascular autonomic function have prognostic value in the current era of pharmacological therapy recommended for DM patients with coexisting coronary artery disease (CAD), which consists of drugs that affect autonomic balance, i.e. angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), beta-blockers, and statins.. We studied 127 consecutive patients with type 2 DM and angiographically documented stable CAD (age: 64 years, women: 28%, treatment: ACEI/ARBs: 100%, statins: 98%, beta-blockers: 88%, insulin therapy: 46%). The assessment of autonomic balance within the cardiovascular system included heart rate variability (HRV) (time and spectral-domain analyses) and non-invasive evaluation of baroreflex sensitivity (sequence and controlled breathing methods). Primary end-points were cardiovascular mortality and urgent hospital admissions due to cardiovascular symptoms.. During the mean follow-up of 502 +/- 161 days, 28 patients (22%) experienced a cardiovascular event: 7 died and 21 were admitted to hospital. We found the following predictors of an increased risk of the combined end point (cardiovascular death and hospitalisation): elevated level of N-terminal BNP (for log NT-proBNP - HR = 2.6, p = 0.004), severe CAD (3-vessel disease - HR = 2.4, p = 0.02), renal insufficiency (eGFR < 60 ml/min/1.73 m2 - HR = 2.7, p = 0.008), and female gender (HR = 3.2, p = 0.002). None of the indices of autonomic balance had prognostic value (p > 0.2 for all).. In the population of diabetic patients with stable CAD who receive optimal pharmacological therapy, indices of impaired autonomic function are no longer predictors of poor outcome.

Topics: Angina Pectoris; Autonomic Nervous System; Baroreflex; Cardiovascular Diseases; Comorbidity; Coronary Artery Disease; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Diabetic Neuropathies; Electrocardiography; Female; Follow-Up Studies; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Risk Factors; Sex Factors; Treatment Outcome

Urate, a naturally-occurring antioxidant, is a marker/factor for cardiovascular disease. Hyperuricaemia is associated with IR, MetS and endothelial dysfunction. We characterised the associations between neurohormones, uricaemia, and glucose homeostasis in type 2 diabetes mellitus (T2DM) males. Cross-sectional; 705 T2DM males divided into two groups: uric acid < 7.0 mg/dl (normouricaemic; n=476) versus uric acid >or= 7.0 mg/dl (hyperuricaemic; n=229). HOMA beta-cell function (B), insulin sensitivity (S), hyperbolic product (BxS), and (BxS) loss rate were determined alongside neurohormones (Nt-proANP, BNP, Big ET-1 and UII). Mean age and diabetes duration were not different between groups. Hyperuricaemics had more macroangiopathy, total/central adiposity, IR, hypertension, dyslipidemia and MetS prevalence. Nt-proANP and BNP levels were more than twice as high in hyperuricaemics, whereas Big ET-1 and UII were higher by 46% and 14%, respectively. HOMA (BxS) was higher in hyperuricaemics: 31 (16)% vs. 26 (18)% (p=0.0004). BxS loss rate was faster in normouricaemics: 1.36 (0.54)% vs. 1.20 (0.43)%/year(-1) (p<0.0001 ). The proportion with HbA(1C) < 7.0% was 39% (normouricaemics) vs. 49% (hyperuricaemics; p=0.0091). In T2DM males, hyperuricaemia is associated with raised neurohormones together with better beta-cell indices. Urate's dual properties may translate into beneficial (glucose homeostasis) and detrimental (raised neurohormones) effects.

Topics: Aged; Atrial Natriuretic Factor; Biomarkers; Blood Glucose; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Endothelin-1; Glycated Hemoglobin; Humans; Hyperuricemia; Insulin; Insulin-Secreting Cells; Male; Metabolic Syndrome; Middle Aged; Natriuretic Peptide, Brain; Up-Regulation; Uric Acid

To evaluate BNP in assessing LV functions in asymptomatic type 2 diabetic patients.. BNP was measured in 91 consecutive patients with type 2 diabetes mellitus. According to Doppler echocardiography, patients were first separated into three categories: normal LV function, or isolated diastolic or systolic LV dysfunction. As some patients with diastolic dysfunction were treated for hypertension, the population was divided into four groups: groups 1, 2 and 3 all had no antihypertensive treatment, and had normal LV function, and isolated diastolic and systolic LV dysfunction, respectively; and group 4 were being treated with antihypertensive drugs and had diastolic LV dysfunction.. In group 1, BNP levels (13+/-2 ng/L) were lower than in group 2 (87+/-20 ng/L, P<0.0001) or group 3 (213+/-32 ng/L, P<0.0001), but were similar to those of group 4 (32+/-6 ng/L, P=0.14). ROC analysis revealed a rule-out value of 23 ng/L for group 1 versus group 2, and of 239 ng/L for group 2 versus group 3. In groups 1, 2 and 3 taken together, BNP levels were correlated with urinary albumin excretion rate (r=0.80, P<0.0001) and pulse pressure (r=0.65, P<0.0001). In group 4, patients receiving ACE inhibitors had lower BNP levels than those receiving ss-blockers.. BNP can be used to pre-screen asymptomatic type 2 diabetic patients with LV dysfunction, and may reveal vascular remodelling in type 2 diabetes mellitus.

Topics: Aged; Antihypertensive Agents; Biomarkers; Diabetes Mellitus, Type 2; Echocardiography, Doppler; Female; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Regression Analysis; Ventricular Dysfunction, Left

Topics: Adiponectin; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Humans; Molecular Weight; Natriuretic Peptide, Brain; Peptide Fragments; Risk

We assessed the effect of the addition of pioglitazone on metabolic control and heart function of patients with type 2 diabetes already receiving sulfonylurea plus metformin. Forty-four patients were given 30 mg of pioglitazone for 3 months. Physical examination, laboratory tests including N-terminal pro-brain natriuretic peptide (NT-proBNP), and echocardiography, were performed at baseline and at study completion. Target HbA(1c) levels were achieved by 44.2% of the patients. Pioglitazone ameliorated lipid profile and lowered liver enzymes and C-reactive protein. Significant increases in NT-proBNP by 39% (P < 0.005) were noticed, but echocardiographic parameters were not altered, even in high-risk subgroups (patients older than 60 years, with diabetes for more than 10 years, with hypertension, with elevated baseline NT-proBNP levels, with left ventricular hypertrophy). In patients with a greater than 60% increase in NT-proBNP levels, a significant increase in left ventricular ejection fraction (P < 0.05) and in fractional shortening (P < 0.05) was found. None of the patients developed edema or signs or symptoms of heart failure. Triple oral combination antidiabetic treatment is an effective therapeutic strategy and weight gain does not abrogate its beneficial actions. Pioglitazone does not affect heart function and even though it increases NT-proBNP, this appears to represent a reaction to volume overload.

Topics: Adult; Aged; Blood Glucose; C-Reactive Protein; Diabetes Mellitus, Type 2; Echocardiography; Female; Heart; Humans; Hypoglycemic Agents; Lipids; Liver Function Tests; Male; Metformin; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Pioglitazone; Thiazolidinediones

Topics: Aged; Antigens, CD34; Blood Pressure; Cell Count; Diabetes Mellitus, Type 2; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain

To date, several different equations to predict the glomerular filtration rate (GFR) in patients with renal insufficiency have been developed for different patients groups. Our aim was to determine the prognostic factors of GFR in our homogenous patient group of obese, water-loaded patients with Type 2 diabetes and renal insufficiency, since we assumed that the endogenous creatinine clearance (ECC) alone may not be an accurate method to predict GFR.. We recruited 46 obese patients (37 men) with Type 2 diabetes and renal insufficiency in our nephrology center in Mettmann (Germany). However, two male patients were excluded from the analysis due to an outlying insulin level or low inulin clearance. The inulin clearance as a measure of renal function performed by the single shot method was compared with the GFR estimated by ECC, Cystatin C, and MDRD formula. Several multiple regression models were built to test the impact of the prognostic factors age, sex, body mass index (BMI), insulin resistance according to the homeostasis model assessment (HOMA), body water (TBW), brain natriuretic peptide (BNP), and proteinuria on the inulin clearance. In the main regression model to predict the inulin clearance by ECC, only the statistically significant prognostic factors of these models were selected, as well as the interaction between GFR predicted by ECC (GFR_ECC) and BMI.. The prognostic factors GFR_ECC, age, BMI, HOMA and proteinuria had a statistically significant impact on the inulin clearance (the gold standard of the GFR) in our patient population (p < 0.05). However, the interaction of GFR_ECC and BMI was not significant (p = 0.06) in our model. The model was validated and considered well-fitted with a coefficient of determination (R2) of 0.69.. The independent prognostic factors to determine GFR in obese, water-loaded diabetic patients are GFR_ECC, age, BMI, HOMA and proteinuria. However, our model should be revalidated and tested in a larger sample size to probably detect an interaction between GFR_ECC and BMI as an additional prognostic factor.

Topics: Age Factors; Aged; Blood Pressure; Body Mass Index; Creatinine; Diabetes Mellitus, Type 2; Disease Progression; Female; Glomerular Filtration Rate; Humans; Insulin; Insulin Resistance; Male; Natriuretic Peptide, Brain; Nephelometry and Turbidimetry; Obesity; Prognosis; Proteinuria; Renal Insufficiency

We sought to determine N-terminal pro-Brain Natriuretic Peptide (NTproBNP) levels among a population of individuals with type 2 diabetes, and to correlate these levels with diabetes medications and patient demographics.. We analyzed data from 506 patients with type 2 diabetes. We compared NT-proBNP levels of these patients with those from the general population. We also sought to determine whether patients' NT-proBNP levels were correlated with diabetes medications, age, gender, creatinine, hemoglobin A1C levels, BMI, blood pressure, and lipid levels.. Increasing doses of sulfonylureas were associated with increasing levels of NT-proBNP. However, patients on combined sulfonylurea and metformin therapy had lower NT-proBNP levels than those on sulfonylureas alone. Neither thiazolidinediones nor insulin were associated with NT-proBNP levels. The majority of patients with type 2 diabetes had similar NT-proBNP levels compared to a reference group from the general population. In no age category did NT-proBNP levels differ significantly between men and women. Levels of NT-proBNP were positively associated with age (p<0.0001), systolic blood pressure (p<0.01) and creatinine levels (p<0.0001), and negatively associated with diastolic blood pressure (p<0.001). Levels of NT-proBNP were not associated with A1C, BMI, triglycerides, and high density lipoprotein (p=NS).. Levels of NT-proBNP are associated with increasing sulfonylurea dosage, age, blood pressure, and creatinine levels. There is unlikely to be clinically significant differences in NT-proBNP levels between patients with type 2 diabetes and a normal population.

Topics: Administration, Oral; Adult; Age Factors; Aged; Aged, 80 and over; Analysis of Variance; Biomarkers; Blood Glucose; Case-Control Studies; Cohort Studies; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Linear Models; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Probability; Reference Values; Risk Assessment; Sex Factors; Sulfonylurea Compounds; Treatment Outcome

Left ventricular (LV) diastolic dysfunction has been reported to be prevalent in diabetic subjects, but this recognition could often be missed. We evaluated prevalence of LV diastolic dysfunction and diagnostic utility of brain-natriuretic peptide (BNP) in asymptomatic patients with type 2 diabetes mellitus.. Plasma BNP levels and LV geometry and diastolic filling indices, including the ratio of peak early transmitral Doppler flow (E) over flow propagation velocity (Vp) measured by colour M-mode Doppler echocardiography, were analysed in 98 consecutive asymptomatic patients with type 2 diabetes mellitus and 51 age-matched controls.. The LV mass index and relative wall thickness were higher in diabetic groups than controls without any differences in LV systolic function. The frequency of diastolic dysfunction defined as E/Vp > or = 1.5 were 31% in diabetic groups and 15% in controls (chi(2) = 4.364, p = 0.037). By receiver-operating characteristic (ROC) curve analysis, a BNP cutoff value of 19.2 pg/ml in controls had a 53.1% positive predictive value (53.1%) and a high negative predictive value (94.4%) for E/Vp >/= 1.5, whereas a BNP cutoff value of 18.1 pg/ml in diabetic groups had a 61.8% positive and 97.3% negative predictive values.. The frequency of E/Vp > or = 1.5 was higher in asymptomatic diabetic patients, suggesting that LV diastolic dysfunction was prevalent. The plasma concentration of BNP could be used to depict LV diastolic dysfunction in such population.

Topics: Biomarkers; Blood Pressure; Diabetes Mellitus, Type 2; Echocardiography, Doppler, Color; Female; Heart Ventricles; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; ROC Curve; Ventricular Dysfunction, Left

Plasma N-terminal proBNP (NT-proBNP) is released in response to pressure overload, intravascular volume expansion and myocardial ischemia from cardiac ventricles. We studied the relationship between NT-proBNP levels and left ventricular dysfunction and urinary albumin excretion in Type 2 diabetes. The study group consisted of 130 diabetic patients referred for echocardiography. They were divided into four groups according to echocardiographic finding and into three groups according to urinary albumin excretion. NT-proBNP levels were measured by electrochemiluminescence. There were significant differences in NT-proBNP levels among four groups (P=0.012), with a highly significant difference between normal and other groups with left ventricular dysfunction. NT-proBNP levels in diastolic dysfunction were significantly higher than normal group (1491.1 pg/mL versus 232.3 pg/mL, P=0.01), even though there was no difference in ejection fraction (EF) (61.2+/-7.9% versus 60+/-8.4%, P=0.773). NT-proBNP levels showed positive correlation with age (Rs=0.37, P<0.001), creatinine (Rs=0.38, P=0.001), LVIDS (Rs=0.56, P=0.001) and LVIDD (Rs=0.34, P=0.04) and negative correlation with EF (Rs=-0.66, P=0.001). NT-proBNP levels significantly differed among three groups according to urinary albumin excretion (P=0.031). These results suggest that NT-proBNP could be used to identify any impairment of left ventricular function in diabetes.

Topics: Aged; Albuminuria; Blood Pressure; Body Mass Index; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Echocardiography; Female; Humans; Lipids; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Ventricular Dysfunction, Left

Topics: Administration, Oral; Aged; Biomarkers; Cardiovascular Diseases; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Neuropathies; Humans; Hypoglycemic Agents; Insulin; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments

Topics: Age Factors; Animals; Biomarkers; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Heart Failure; Humans; Male; Mice; Natriuretic Peptide, Brain; Rats; Sex Factors

Appropriate tools are necessary for predicting cardiovascular events in patients with diabetes mellitus because of their high incidence. In this study, we assessed whether a combination of brain natriuretic peptide (BNP) and C-reactive protein (CRP) measurement were useful prognosticators in patients with type 2 diabetes mellitus. One hundred and nine patients with type 2 diabetes mellitus, aged 52 to 93 years, were examined at outpatient clinics for blood, urinary samples, and echocardiography. They were then followed prospectively. During the average follow-up period of 30 months (range, 3 to 37), 15 patients (14%) had cardiovascular events: This was the first event in 5 patients and a recurrence in 10. Cox regression analysis showed that the past event (hazard ratio [HR] 4.819 [95% confidence interval (CI): 1.299-17.881]; p = 0.019) and plasma BNP level (HR 1.007 [95% CI: 1.002-1.012]; p = 0.010] were independently significant factors for the cardiovascular events during the follow-up period. Patients with plasma BNP > or =53 pg/mL and CRP > or =0.95 mg/dL demonstrated the highest incidence in cardiovascular event, compared to those categorized into either or both low levels of BNP and CRP. This study suggests that combination of plasma BNP and CRP measurement provides the additive prognostic information of cardiovascular events in patients with type 2 diabetes mellitus.

Topics: Aged; Aged, 80 and over; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Epidemiologic Methods; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Outpatients; Prognosis; Risk Assessment; Ultrasonography, Doppler, Color

Plasma brain natriutetic peptide (BNP) concentrations in type 2 diabetic patients were measured by newly developed enzyme immunoassay, and their clinical application was evaluated. Precision of the measurement system was satisfactory for clinical use, and the value obtained by this system had good correlation to that by radioimmunoassay. Tubes containing NaF in addition to EDTA, usually used for measurement of plasma glucose and HbA1c in diabetic patients, could be used for the collection of plasma sample. In 133 type 2 diabetic patients who had no symptom for heart failure, plasma BNP was elevated in those with ischemic heart disease and it was also significantly elevated even in the patients who had no ischemic change on double Master two-step exercise testing than that in control subjects. In 52 patients receiving the examination by cardiosonography, plasma BNP levels significantly correlated to the left ventricular mass index, and also had a significant correlation to peak flow velocity in early diastole/peak flow velocity in late diastole (E/A) ratio, one of a simple index for an asymptomatic diastolic heart failure. Multiple logistic regression analysis revealed that age and coronary heart disease were extracted as a significant valuable for plasma BNP level in type 2 diabetic patients. These results suggest that measurement of plasma BNP in type 2 diabetic patients was useful as a screening method for evaluating the latent deterioration of heart function such as asymptomatic ischemic heart disease.

Topics: Diabetes Mellitus, Type 2; Female; Humans; Immunoenzyme Techniques; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain

We examined the usefulness of BNP for screening for left ventricular (LV) diastolic dysfunction in a sample of type 2 diabetic patients, without structural heart disorder, who have never presented symptoms or signs of heart failure (HF).. Seventy-six consecutive patients admitted to the Outpatient Diabetes Clinic were studied. Blood samples were analyzed using the Triage BNP fluorescence immunoassay (Biosite Diagnostics, La Jolla, CA, USA). Echocardiography examinations were performed, with no knowledge of the BNP value. A total of 39 patients out of 76 (51%) were diagnosed with LV diastolic dysfunction and 23 (30%) with LV hypertrophy. Of the patients with LV diastolic dysfunction, impaired relaxation and pseudonormal pattern accounted for 97 and 3% of the cases, respectively. BNP levels among subjects with LV diastolic dysfunction (26+/-22 pg/ml, n=39) were not significantly different from patients with normal LV function (24+/-23 pg/ml, n=37 pg/ml; Mann-Whitney U-test, Z=-0.4, n.s.).. Our data confirm alarmingly high prevalence of LV diastolic dysfunction in asymptomatic individuals with diabetes. Identification of patients with preclinical diabetic cardiomyopathy should be a research and clinical priority. BNP levels cannot be used to detect mild LV diastolic dysfunction in this subset of patients, which requires Doppler echocardiography to be detected.

Topics: Aged; Analysis of Variance; Biomarkers; Case-Control Studies; Creatinine; Diabetes Mellitus, Type 2; Diastole; Echocardiography, Doppler; Female; Fluorescence Polarization Immunoassay; Humans; Hypertrophy, Left Ventricular; Male; Middle Aged; Natriuretic Peptide, Brain; Sensitivity and Specificity; Severity of Illness Index; Ventricular Dysfunction, Left

Anaemia is common in patients with diabetes and associated with an increased risk of diabetic complications. Although the role of anaemia in heart failure is established, we hypothesize that anaemia also contributes to an increased risk of cardiac dysfunction in patients with Type II diabetes. In the present study, 228 consecutive adults with diabetes were investigated using transthoracic echocardiography. Echocardiographic parameters were correlated with the Hb (haemoglobin) level and adjusted for other risk factors for cardiac dysfunction using multivariate analysis. More than one in five patients (23%) had anaemia, which was an independent risk factor for cardiac dysfunction on echocardiography. Over one-third of all patients with evidence of abnormal cardiac function (diastolic and/or systolic dysfunction) on echocardiography had anaemia compared with <5% of patients with normal echocardiographic findings. Most patients with anaemia had cardiac dysfunction (94%), with the major abnormality being diastolic dysfunction associated with an increased left ventricular mass and impaired relaxation indices. A continuous association between diastolic function and Hb was also observed in patients without anaemia. In patients with a history of cardiovascular disease, systolic dysfunction was twice as common in patients with anaemia. Anaemia was also correlated with plasma markers of cardiac risk, including BNP (brain natriuretic peptide), CRP (C-reactive protein) and AVP (arginine vasopressin). Notably, the predictive utility of these markers was eliminated after adjusting for Hb. Consequently, the inexpensive measurement of Hb may be a useful tool to identify diabetic patients at increased risk of cardiac dysfunction.

Topics: Aged; Anemia; Arginine Vasopressin; Biomarkers; C-Reactive Protein; Diabetes Complications; Diabetes Mellitus, Type 2; Diastole; Female; Heart Diseases; Hemoglobins; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Ultrasonography

The present study tested the hypothesis that increased plasma brain natriuretic peptide (BNP) levels are related to cardiac autonomic dysfunction in type 2 diabetic patients. A total of 32 consecutive Japanese patients with type 2 diabetes were assigned to either a high-BNP (>or=18 pg/ml) group (n=12; age 57+/-13 years, mean+/-S.D.) or a normal-BNP (<18 pg/ml) group (n=20; 59+/-10 years). No patient had any overt structural heart disease. Cardiac autonomic function was assessed by measurements of baroreflex sensitivity (BRS), heart rate variability (HRV) and cardiac (123)I-metaiodobenzylguanidine (MIBG) scintigraphic findings. BRS was lower (p<0.005) in the high-BNP group than in the normal-BNP group. However, the components of HRV, and the early and delayed myocardial uptake of (123)I-MIBG and percentage washout rate of (123)I-MIBG were not significantly different between the groups. The plasma level of BNP negatively correlated with BRS (r=0.35, p=0.049). These findings suggest that increased plasma BNP levels were related to cardiac reflex parasympathetic dysfunction in our Japanese type 2 diabetic patients.

Topics: 3-Iodobenzylguanidine; Adult; Aged; Autonomic Nervous System; Baroreflex; Blood Glucose; Blood Pressure; Diabetes Mellitus, Type 2; Echocardiography; Female; Heart; Heart Conduction System; Heart Rate; Humans; Hypoglycemic Agents; Insulin; Iodine Radioisotopes; Lipids; Male; Middle Aged; Natriuretic Peptide, Brain; Radionuclide Imaging

To find out whether B-type natriuretic peptide (BNP) detects silent myocardial ischaemia in patients with type 2 diabetes, since many of these patients have silent ischaemia leading to unexpected cardiac deaths.. Prospective cross-sectional study with consecutive recruitment of patients.. Outpatient, single centre.. 219 patients with type 2 diabetes. Patients were excluded if they had a history or evidence of cardiac failure.. BNP, echocardiography and exercise tolerance test (ETT). BNP was compared with the ETT result in all patients and specifically in those who had no apparent ischaemic heart disease (IHD).. 121 patients had no history of IHD or cardiac failure and of these patients 85 had a clearly abnormal or normal ETT result. BNP was higher in patients with an abnormal than with a normal ETT (mean 58.2 (SD 46.3) v 24.4 (SD 15.7) pg/ml, p < 0.001). In univariate analysis BNP was an independent predictor of an abnormal ETT (p < 0.001). In multivariate analysis BNP remained an independent predictor of the ETT result. BNP concentration over 20 pg/ml predicted an abnormal ETT result with a sensitivity of 87% and specificity of 37%, and BNP over 40 pg/ml had a sensitivity of 63% and a specificity of 81%.. BNP is of value in predicting silent ischaemia on exercise testing in asymptomatic patients with type 2 diabetes.

Topics: Area Under Curve; Biomarkers; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Exercise Test; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Prospective Studies; Sensitivity and Specificity; Ventricular Dysfunction, Left

Raised N-terminal pro-B-type natriuretic peptide (NT-proBNP) is associated with a poor cardiac outcome in non-diabetic populations. Elevated NT-proBNP predicts excess morbidity and mortality in diabetic patients with an elevated urinary albumin excretion rate. This study investigated the prognostic value of NT-proBNP in a cohort of type 2 diabetic patients.. In a prospective observational follow-up study, 315 type 2 diabetic patients with normoalbuminuria (n=188), microalbuminuria (n=80) and macroalbuminuria (n=47) at baseline were followed for a median (range) of 15.5 (0.2-17.0) years. Plasma NT-proBNP concentrations were determined by immunoassay at baseline. Endpoints were overall and cardiovascular mortality.. Of the patients, 162 died (51%), 119 of them (74%) due to cardiovascular causes. All-cause mortality was increased in patients with NT-proBNP in the second and third tertiles (hazard ratios [95% CI] compared with the first tertile, 1.70 [1.08-2.67] and 5.19 [3.43-7.88], p<0.001). These associations persisted after adjustment for urinary albumin excretion rate, glomerular filtration rate and conventional cardiovascular risk factors (covariate adjusted hazard ratios 1.46 [0.91-2.33] and 2.54 [1.56-4.14], p<0.001). This increased mortality was attributable to more cardiovascular deaths in the second and third NT-proBNP tertile (unadjusted hazard ratios 1.63 [0.96-2.77] and 4.88 [3.01-7.91], p<0.001; covariate adjusted 1.37 [0.79-2.37] and 2.26 [1.27-4.02], p=0.01). When patients with normo-, micro- and macroalbuminuria were analysed separately, NT-proBNP levels above the median (62 ng/l) were consistently associated with increased overall and cardiovascular mortality in all three groups (p<0.001).. In patients with type 2 diabetes, elevated circulating NT-proBNP is a strong predictor of the excess overall and cardiovascular mortality, this predictor status being independent of urinary albumin excretion rate and conventional cardiovascular risk factors.

Topics: Albuminuria; Creatinine; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Nephropathies; Diabetic Retinopathy; Female; Follow-Up Studies; Glomerular Filtration Rate; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prospective Studies; Survival Analysis; Time Factors

We examined whether plasma N-terminal probrain natriuretic peptide (NT-proBNP) predicts cardiovascular outcome in patients with type 2 diabetes.. A total of 160 microalbuminuric type 2 diabetic patients (mean age 55.1 years [SD 7.2], 119 men) were enrolled in the Steno-2 Study examining the effect of multifactorial treatment, and were divided into two groups according to baseline levels of plasma NT-proBNP below or above the median for the cohort, which was followed for an average of 7.8 years. Cardiovascular outcome was a composite of cardiovascular mortality, myocardial infarction, stroke, revascularisation procedures in the heart or legs, and amputations.. In the whole group, plasma NT-proBNP being above the median was associated with an increased risk of cardiovascular disease during follow-up, with an unadjusted hazard ratio of 4.4 (95% CI 2.3-8.4; p<0.0001). A decrease in plasma NT-proBNP of 10 pg/ml during the first 2 years of intervention was associated with a 1% relative reduction in the primary endpoint (p<0.001). Despite polypharmacological treatment targeting cardiovascular disease, the mean plasma NT-proBNP level increased during follow-up.. We conclude that high plasma NT-proBNP is a major risk marker for cardiovascular disease in patients with type 2 diabetes and microalbuminuria.

Topics: Albuminuria; Biomarkers; Blood Pressure; Cardiovascular Diseases; Cohort Studies; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptide Fragments; Proportional Hazards Models; Smoking; Time Factors

To examine levels of NT-proBNP and its relation to hypertension, as well as diastolic function in normoalbuminuric patients with Type 2 diabetes.. The study comprised 60 Type 2 diabetic patients without albuminuria. Thirty patients were normotensive and 30 had hypertension. Exclusion criteria were cardiac symptoms and an ejection fraction < 55%. Thirty age- and sex-matched normal subjects served as controls. Diastolic dysfunction was assessed with echocardiography, by means of mitral inflow and colour M-Mode flow propagation recordings.. Overall NT-proBNP was significantly elevated in the Type 2 diabetes group, compared with the controls [54.5 pg/ml (5-162) vs. 32.7 pg/ml (5-74.3) P = 0.02]. NT-proBNP was significantly higher among hypertensive patients compared with both normotensive patients and controls but no difference was found between the normotensive patients and the controls [58.0 pg/ml (8.5-162), P < 0.05 vs. 50.8 pg/ml (5-131) P = 0.4]. Patients with concentric and eccentric hypertrophy had significantly higher NT-proBNP levels compared with the control group [81.0 pg/ml (5-147), P < 0.001 and 66.8 pg/ml (42-128), P < 0.001], whereas patients with left ventricular remodelling (enlarged relative wall diameter but normal left ventricular mass) were comparable with the control group [42.3 pg/ml (8.3-142) P = 0.55]. Patients with left atrial enlargement also had incremental NT-proBNP values. NT-proBNP was only moderately correlated to age (r = 0.33, P < 0.05) and left ventricular diastolic diameter (r = 0.41, P < 0.05), but unrelated to diastolic function.. NT-proBNP is significantly increased in hypertensive, normoalbuminuric patients with Type 2 diabetes. These findings were related to left ventricular hypertrophy and increased left atrial and ventricular diameters.

Topics: Albuminuria; Cardiomyopathy, Dilated; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diastole; Female; Heart Atria; Heart Ventricles; Humans; Hypertrophy, Left Ventricular; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptide Fragments

We recently showed that plasma concentration of N-terminal atrial natriuretic peptide (Nt-proANP) is strongly directly related to salt sensitivity. The aims of the present study were to test (i) whether plasma concentration of N-terminal brain natriuretic peptide (Nt-proBNP) is related to salt sensitivity and (ii) whether Nt-proANP, as a marker of salt sensitivity, differs between type 2 diabetes patients and nondiabetic subjects without a history of coronary heart disease.. Nt-proBNP was determined in 30 Swedish normal subjects with heredity for primary hypertension and salt sensitivity was defined as the difference between mean arterial blood pressure after 1 week on a high-salt diet (240 mmol day(-1)) and 1 week on a low-salt diet (10 mmol day(-1)). Nt-proANP was measured in 253 patients with type 2 diabetes and in 230 nondiabetic subjects aged 40-70 years, all without a history of coronary heart disease.. Amongst the 30 subjects, in whom salt sensitivity was directly measured, Nt-proBNP was not correlated with salt sensitivity (R=-0.18, P=0.35). Nt-proANP (median, interquartile range) was lower in patients with type 2 diabetes (505, 387-661 pmol L(-1)) than in nondiabetic subjects (536, 421-696 pmol L(-1)) (P=0.02). In a multiple regression analysis heart rate (P <0.00001), diastolic blood pressure (P=0.02) and diabetes status (P=0.02) were inversely related whereas age (P <0.00001), cystatin C (P=0.0006), hypertension treatment (P=0.002) and female sex (P=0.006) were directly related to ln(Nt-proANP).. In contrast to Nt-proANP, Nt-proBNP is not related to salt sensitivity. Salt sensitivity, as estimated by Nt-proANP, seems to be reduced in type 2 diabetes.

Topics: Atrial Natriuretic Factor; Biomarkers; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptide Fragments; Protein Precursors; Sodium Chloride, Dietary

Topics: Biomarkers; Blood Pressure; Body Mass Index; Diabetes Mellitus, Type 2; Female; Glomerular Filtration Rate; Humans; Kidney Failure, Chronic; Male; Natriuretic Peptide, Brain

The prevalence of left ventricular hypertrophy (LVH), coronary artery disease, and subclinical cardiomyopathy in diabetic patients without known cardiac disease is unclear. We sought the frequency of these findings to determine whether plasma brain natriuretic peptide (BNP) could be used as an alternative screening tool to identify subclinical LV dysfunction.. Asymptomatic patients with diabetes mellitus without known cardiac disease (n = 101) underwent clinical evaluation, measurement of BNP, exercise stress testing, and detailed echocardiographic assessment. After exclusion of overt dysfunction or ischemia, subclinical myocardial function was sought on the basis of myocardial systolic (Sm) and diastolic velocity (Em). Association was sought between subclinical dysfunction and clinical, biochemical, exercise, and echocardiographic variables. RESULTS; Of 101 patients, 22 had LVH and 16 had ischemia evidenced by exercise-induced wall motion abnormalities. Only 4 patients had abnormal BNP levels; BNP was significantly increased in patients with LVH. After exclusion of LVH and coronary artery disease, subclinical cardiomyopathy was identified in 24 of 66 patients. Subclinical disease could not be predicted by BNP.. Even after exclusion of asymptomatic ischemia and hypertrophy, subclinical systolic and diastolic dysfunction occurs in a significant number of patients with type 2 diabetes. However, screening approaches, including BNP, do not appear to be sufficiently sensitive to identify subclinical dysfunction, which requires sophisticated echocardiographic analysis.

Topics: Aged; Cardiomyopathies; Coronary Disease; Diabetes Complications; Diabetes Mellitus, Type 2; Echocardiography, Doppler; Exercise Test; Female; Humans; Hypertrophy, Left Ventricular; Male; Middle Aged; Natriuretic Peptide, Brain; Observer Variation; Ventricular Dysfunction, Left

This study investigates whether the plasma brain natriuretic peptide (BNP) level is increased by the clinical traits of diabetes, including its complications, and whether these levels are affected by the presence of other combined diseases such as hypertension, hyperlipidemia, and coronary heart disease (CHD) in patients with diabetes. In 223 patients with Type 2 diabetes, the mean value of plasma BNP reached 32.3+/-4.1 pg/mL. The levels significantly increased with age, hypertension, and CHD but not with the duration of diabetes, HbA1c level, or hyperlipidemia. With regard to the type of therapy, the BNP levels were significantly lower in the combinations of both sulfonylurea and metformin and sulfonylurea and pioglitazone than those in insulin alone. In addition, the BNP levels in the group with diabetic complications, including retinopathy and nephropathy, and macroalbuminuria were significantly elevated in comparison with those without these complications and macroalbuminuria. Interestingly, however, no difference was observed between these groups after removal of the values in patients with CHD. These results have clarified that the plasma BNP levels in diabetic patients could increase only by the progression of macrovascular diseases, such as CHD, but not by the current diabetic control or diabetic microvascular complications.

Topics: Age Factors; Aged; Aged, 80 and over; Albuminuria; Antihypertensive Agents; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hyperlipidemias; Hypertension; Hypoglycemic Agents; Male; Middle Aged; Natriuretic Peptide, Brain

In this study we examined diabetes- and hypertension-induced changes in cardiac structure and function in an animal model of type 2 diabetes, the Goto-Kakizaki (GK) rat. We hypothesized that treatment with omapatrilat, a vasopeptidase inhibitor, which causes simultaneous inhibition of angiotensin converting enzyme and neutral endopeptidase, provides additional cardioprotective effects, during normal- as well as high sodium intake, compared to treatment with enalapril, a selective inhibitor of angiotensin converting enzyme. Fifty-two GK rats were randomized into 6 groups to receive either normal-sodium (NaCl 0.8%) or high-sodium (NaCl 6%) diet and enalapril, omapatrilat or vehicle for 12 weeks. The GK rats developed hypertension, cardiac hypertrophy and overexpression of cardiac natriuretic peptides and profibrotic connective tissue growth factor compared to nondiabetic Wistar rats. The high dietary sodium further increased the systolic blood pressure, and changed the mitral inflow pattern measured by echocardiography towards diastolic dysfunction. Enalapril and omapatrilat equally decreased the systolic blood pressure compared to the control group during normal- as well as high-sodium diet. Both drugs had beneficial cardioprotective effects, which were blunted by the high dietary sodium. Compared to enalapril, omapatrilat reduced the echocardiographically measured left ventricular mass during normal-sodium diet and improved the diastolic function during high-sodium diet in GK rats. Furthermore, omapatrilat reduced relative cardiac weight more effectively than enalapril during high sodium intake. Our results suggest that both the renin-angiotensin and the neutral endopeptidase system are involved in the pathogenesis of diabetic cardiomyopathy since vasopeptidase inhibition was shown to provide additional benefits in comparison with selective angiotensin converting enzyme inhibition alone.

Topics: Aldosterone; Angiotensin-Converting Enzyme Inhibitors; Animals; Atrial Natriuretic Factor; Blood Glucose; Blood Pressure; Body Weight; Cardiomegaly; Collagen; Diabetes Mellitus, Type 2; Echocardiography; Enalapril; Fibrosis; Heart; Insulin; Male; Metalloendopeptidases; Myocardium; Natriuretic Peptide, Brain; Organ Size; Protease Inhibitors; Pyridines; Random Allocation; Rats; Rats, Wistar; RNA, Messenger; Sodium Chloride, Dietary; Thiazepines

Cardiovascular risk scores are available but are often not calculated in busy clinics for numerous practical reasons. B-type natriuretic peptide (BNP) may be an alternative way of identifying subjects who have a high total cardiovascular risk score. We compared BNP level with Framingham 10-year Risk Scores for coronary heart disease and stroke and New Zealand Cardiovascular Risk Scores in 231 patients who had type 2 diabetes and no preexisting coronary heart disease or stroke. There was a significant correlation between log BNP and 10-year risk for coronary heart disease and stroke, and there were significantly higher BNP levels in those who had high cardiovascular risk as assessed by the New Zealand Risk Score. BNP may be a useful way of measuring total cardiovascular risk, thus having the potential to better target the most aggressive primary preventive therapies toward the most needy.

Topics: Adult; Aged; Biomarkers; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Humans; Middle Aged; Natriuretic Peptide, Brain; Risk Assessment; Risk Factors

The plasma levels of either brain natriuretic peptide (BNP) or the N-terminal fragment of the prohormone (NT-proBNP) have recently gained extreme importance as markers of myocardial dysfunction. Patients with type 2 diabetes are at high risk of developing cardiovascular complications. This study was aimed to assess whether plasma NT-proBNP levels are at similar levels in type 2 diabetics with or without overt cardiovascular diseases.. We assayed plasma NT-proBNP in 54 type 2 diabetics, 27 of whom had no overt macro- and/or microvascular complications, while the remaining ones had either or both. The same assay was carried out in 38 healthy control subjects age and sex matched as a group with the diabetics.. Plasma NT-proBNP was higher in diabetics (median 121 pg/ml, interquartile range 50-240 pg/ml, ) than in those without complications (37 pg/ml, 21-54 pg/ml, P<0.01). Compared with the controls (55 pg/ml, 40-79 pg/ml), only diabetics with vascular complications had significantly increased plasma NT-proBNP levels (P<0.001). In the diabetics, coronary heart disease and nephropathy (defined according to urinary excretion of albumin) were each independently associated with elevated values of plasma NT-proBNP.. In type 2 diabetes mellitus, patients with macro- and/or micro-vascular complications exhibit an elevation of plasma NT-proBNP levels compared to corresponding patients with no evidence of vascular disease. The excessive secretion of this peptide is independently associated with coronary artery disease and overt nephropathy. The measurement of circulating NT-proBNP concentration may therefore be useful to screen for the presence of macro- and/or microvascular disease.

Topics: Blood Pressure; Body Mass Index; Coronary Disease; Diabetes Complications; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Obesity; Peptide Fragments; Reference Values

B-type natriuretic peptide (BNP) increases the risk of death and cardiovascular events in patients without heart failure, even at BNP values within the "normal" range. The reasons for this are unclear.. We performed two separate studies (n = 33 and n = 129) on subjects with type 2 diabetes mellitus in whom frank left ventricular systolic dysfunction had been excluded to ascertain whether a high-normal BNP could be identifying either greater augmentation of the ascending aortic pressure wave, increased left ventricular mass, or a subtly lower left ventricular ejection fraction (but within the normal range).. Our results demonstrate that an increased augmentation index is an independent predictor of BNP levels even when BNP levels are within the normal range (P = .006 in study one and P = .007 in study two). A high-normal BNP also correlated with increased left ventricular mass and (P = .021) with a subtly lower left ventricular ejection fraction (P < .001).. We found that high-normal BNP levels identified increased augmentation of the ascending aortic pressure wave as well as subtle left ventricular abnormalities.

Topics: Aged; Aorta; Diabetes Mellitus, Type 2; Female; Humans; Hypertrophy, Left Ventricular; Male; Middle Aged; Natriuretic Peptide, Brain; Stroke Volume; Ultrasonography; Ventricular Dysfunction, Left

The NH(2)-terminal portion of the precursor of brain natriuretic peptide (Nt-proBNP) has been reported to be elevated in left ventricular dysfunction. This peptide is a split product from the proBNP molecule, and its level in the circulation is not, as the mature BNP peptide, dependent on the peripheral number of BNP receptors. We aimed to test the hypothesis that asymptomatic left ventricular dysfunction (ALVD), as estimated by Nt-proBNP, would be more prevalent in patients with type 2 diabetes without overt cardiovascular disease in comparison with matched control subjects.. The study population consisted of 253 patients with type 2 diabetes and 230 matched control subjects aged 40-70 years without any overt heart disease from primary care centers in Western Finland and Southern Sweden. Nt-proBNP was measured in plasma by competitive enzyme immunosorbent assay.. Patients with type 2 diabetes were shown to have higher Nt-proBNP values (360.9 pmol/l [262.6-467.9]) than control subjects (302.7 pmol/l [215.4-419.2]) (P < 0.001). Nt-proBNP levels were independently related to diabetes after adjustment for age, sex, systolic and diastolic blood pressure, BMI, heart rate, drug treatment, serum creatinine, and cystatin C.. Our data suggest that the secretion of Nt-proBNP is increased in type 2 diabetic patients with no overt heart disease, suggesting that type 2 diabetes is associated with a higher prevalence of ALVD than hitherto thought. Nt-proBNP may thus serve as a screening instrument to select patients with type 2 diabetes who could benefit from an echocardiographical examination.

Topics: Adult; Aged; Diabetes Mellitus, Type 2; Finland; Humans; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptide Fragments; Protein Precursors; Reference Values; Sweden

We hypothesized that B-type natriuretic peptide (BNP) levels can predict cardiac mortality in diabetic patients.. Detection of cardiovascular disease in diabetics can be difficult until overt events occur.. A total of 482 diabetics (majority male with type 2 diabetes) at the Veterans Affairs Medical Center San Diego were divided into two groups: 1) referred patients for echocardiogram on the basis of clinical suspicion of cardiac dysfunction (referred [R], n = 180); 2) patients randomly selected from the diabetic clinic without any suspicion of cardiac dysfunction (not referred [N-R], n = 302). We examined cardiac events and all-cause mortality in relation to initial BNP levels during the follow-up.. A total of 71 (14.7%) patients died during this period: 52 of 180 (29%) in the R group (30 of 52 [58%] cardiac, 10 of 52 [19%] non-cardiac, 2 of 52 [4%] renal, 10 of 52 [19%] unknown cause) and 19 of 302 (6%) in N-R group (6 of 19 [32%] cardiac). The median BNP level in the R and N-R groups who died of cardiac, non-cardiac, and unknown cause was 537 and 87, 80 and 53, and 343 and 38 pg/ml, respectively. The receiver-operating characteristic (ROC) values for mortality in two groups in relation to BNP revealed the area under the curve to be 0.720 and 0.691, respectively (p < 0.01 in both). Among commonly used prognostic indicators in diabetics, only the ROC for triglycerides was significant. The most accurate cut-point in both the N-R group (87%) and R group (61%) was 120 pg/ml of BNP. Cox regression analysis showed BNP to be the most significant predictor of all-cause mortality in the R group. There was a marked decrease in survival in the patient group with BNP >120 pg/ml.. B-type natriuretic peptide appears to be a reliable predictor of future cardiac and all-cause mortality in diabetic patients.

Topics: Adult; Aged; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Prognosis; Prospective Studies; ROC Curve; Sensitivity and Specificity; Triglycerides

Routine screening of diabetic patients with echocardiography is not feasible due to its limited availability and high cost. B-type natriuretic peptide (BNP) is secreted from the left ventricle in response to pressure overload and is elevated in both systolic and diastolic dysfunction.. BNP levels were compared to echocardiographic findings in 263 patients. Patients were divided into two groups: clinical indication for echocardiography (CIE) (n = 172) and those without clinical indication for echocardiography (no-CIE) (n = 91). Cardiologists making the assessment of left ventricular function were blinded when measuring plasma levels of BNP.. The 91 patients with no-CIE with echoes had similar BNP levels (83 +/- 16 pg/ml) to the 215 patients with no-CIE without echoes (63 +/- 10, P = 0.10). Patients with CIE and subsequent abnormal left ventricular function (n = 112) had a mean BNP concentration of 435 +/- 41 pg/ml, compared with those with no-CIE, but had abnormal left ventricular function on echo (n = 32) (161 +/- 40 pg/ml). Twenty-one of 32 patients with no-CIE but with abnormal left ventricular function had diastolic dysfunction (BNP 190 +/- 60 pg/ml). A receiver-operating characteristic (ROC) curve revealed that the area under the curve was 0.91 for CIE patients and 0.81 for no-CIE patients (P < 0.001). For those with no congestive heart failure (CHF) symptoms, BNP levels showed a high negative predictive value (91% for BNP values <39 pg/ml), while in those patients who had a CIE, BNP levels showed a high positive predictive value for the detection of left ventricular dysfunction (96% with BNP levels >90 pg/ml).. BNP can reliably screen diabetic patients for the presence or absence of left ventricular dysfunction.

Topics: Atrial Fibrillation; Biomarkers; Coronary Disease; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Nephropathies; Echocardiography; Female; Humans; Hypertension; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Ventricular Dysfunction, Left; Ventricular Function, Left

We investigated plasma brain natriuretic polypeptide (BNP) in Type 2 NIDDM patients with albuminuria. This study involved normal control subjects (Controls), hypertensive patients without diabetes mellitus (HT) and Type 2 NIDDM patients. Diabetic patients were divided into 4 groups by urinary albumin index (Alb-I): group I <30; group II 30-149; group III 150-300; group IV >300 mg/g creatinine. BNP levels in group III or IV were significantly higher than in Controls. The diabetic patients were re-divided into 4 groups (DM: with neither diabetic retinopathy (which was one of indicators of microangiopathy) nor hypertension, DM+HT: without diabetic retinopathy and with hypertension, DM+R: with diabetic retinopathy and without hypertension and DM+R+HT: with both diabetic retinopathy and hypertension). The Alb-I levels in DM+HT and DM+R+HT were significantly higher than the Controls, indicating the development of diabetic nephropathy in those groups. BNP levels in DM+HT, DM+R or DM+R+HT were significantly higher than in Controls. This indicates that BNP levels elevate in diabetic patients with increased albuminuria due to hypertension or microangiopathy deteriorating diabetic nephropathy. Elevated plasm BNP may play a pathophysiological role in the development of diabetic nephropathy.

Topics: Albuminuria; Atrial Natriuretic Factor; Blood Glucose; Case-Control Studies; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Glycated Hemoglobin; Humans; Middle Aged; Natriuretic Peptide, Brain

Topics: Biomarkers; Blood Pressure; Diabetes Mellitus, Type 2; Diastole; Humans; Natriuretic Peptide, Brain

Topics: Blood Glucose; Blood Pressure; Diabetes Mellitus, Type 2; Female; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Regression Analysis

Topics: Aldosterone; Atrial Natriuretic Factor; Diabetes Mellitus, Type 2; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Renin

Brain natriuretic peptide (BNP), a member of the natriuretic peptide family, is produced and released from cardiac ventricles. BNP regulates the body fluid volume, blood pressure, and vascular tones through the A-type guanylate cyclase-coupled receptor. The presence of renal dysfunction in patients with diabetes affects the plasma levels of atrial natriuretic peptide (ANP). In the present study, we investigated the plasma levels of BNP and ANP and their relationship in normotensive diabetic patients with normoalbuminuria and microalbuminuria. Forty-seven normotensive lean noninsulin-dependent diabetic patients (31 with normoalbuminuria, 16 with microalbuminuria), with normal cardiac function, and 30 age-matched control subjects were enrolled in this study. The plasma levels of BNP in diabetic patients with microalbuminuria were significantly higher than those in diabetic patients with normoalbuminuria (16.7+/-2.4 vs. 9.6+/-1.3 pg/mL, P<0.01) or normal subjects (16.7+/-2.4 vs. 7.0+/-0.6 pg/mL, P<0.01). There was a significant positive correlation between plasma BNP levels and urinary albumin excretion rate in all diabetic patients (r = 0.58, P<0.0001). There was also a significantly positive correlation between plasma BNP and ANP levels in diabetic patients (r = 0.62, P<0.0001). The increased plasma level of BNP in patients with microalbuminuria and its significant correlation with urinary albumin excretion rate suggest that the elevated circulating levels of BNP are caused by the presence of diabetic nephropathy. Down-regulation of A-type guanylate cyclase-coupled receptor of renal tubules may explain the increased plasma levels of both BNP and ANP in normotensive diabetic patients with microalbuminuria.

Topics: Albuminuria; Atrial Natriuretic Factor; Blood Glucose; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Insulin; Male; Middle Aged; Natriuretic Peptide, Brain; Reference Values

Impaired renal sodium excretion and increased plasma atrial natriuretic peptide (ANP) levels have been reported in patients with hypertension associated with insulin resistance and hyperinsulinemia. To clarify the interrelationship between hyperinsulinemia and plasma natriuretic peptides, we investigated the effects of physiological and non-physiological hyperinsulinemia on the plasma ANP and brain natriuretic peptide (BNP) levels. Plasma immunoreactive insulin (IRI), ANP and BNP levels were determined by a euglycemic-hyperinsulinemic glucose clamp in 20 patients with non-insulin-dependent diabetes mellitus, by a glucose challenge test in 22 normal subjects and by an insulin challenge test in six normal subjects. Both in the glucose clamp and the glucose challenge test, plasma ANP showed a significant increase in association with increased plasma IRI and plasma volume. However, there was no significant correlation between the changes in plasma ANP levels and plasma IRI levels in view of the peak values and the area under the curve of their responses. In addition, the plasma ANP did not show any significant change despite the marked elevation of plasma IRI in the insulin challenge test. There was no significant change in plasma BNP under any of the hyperinsulinemic conditions. These findings provide in vivo evidence for the lack of a direct effect of acute hyperinsulinemia on natriuretic peptides, although the chronic effects of hyperinsulinemia remain to be elucidated.

Topics: Acute Disease; Adult; Atrial Natriuretic Factor; Blood Glucose; Diabetes Mellitus, Type 2; Female; Glucose; Humans; Insulin; Insulin Resistance; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins